Biodegradable endoprostheses and methods for their fabrication

ABSTRACT

The disclosure provides biodegradable implantable devices such as a stent comprising a biodegradable polymeric wherein the polymeric material is treated to control crystallinity and/or Tg. The stent is capable to expand at body temperature in a body lumen from a crimped configuration to a deployed diameter and have sufficient strength to support a body lumen.

CROSS-REFERENCE

This application is a continuation of U.S. patent application Ser. No.14/461,159, filed Aug. 15, 2014, which is a continuation of U.S. patentapplication Ser. No. 13/897,302, filed May 17, 2013, which is acontinuation-in-part of U.S. patent application Ser. No. 13/536,957,filed Jun. 28, 2012, which is a continuation-in-part of U.S. patentapplication Ser. No. 13/473,354, filed May 16, 2012, issued as U.S. Pat.No. 8,323,760, which is in turn a continuation application of U.S.patent application Ser. No. 12/016,085, filed Jan. 17, 2008 and issuedas U.S. Pat. No. 8,182,890 on May 22, 2012, which in turn claims thebenefit of U.S. Provisional Application 60/885,700 filed on Jan. 19,2007; U.S. patent application Ser. No. 13/536,957 is also acontinuation-in-part of U.S. patent application Ser. No. 13/434,555,filed Mar. 29, 2012, which is a divisional application of U.S. patentapplication Ser. No. 12/016,085, filed Jan. 17, 2008 and issued as U.S.Pat. No. 8,182,890 on May 22, 2012, which in turn claims the benefit ofU.S. Provisional Application 60/885,700 filed on Jan. 19, 2007; and U.S.patent application Ser. No. 13/536,957 is also a continuation-in-part ofU.S. patent application Ser. No. 12/016,077, filed Jan. 17, 2008, whichclaims the benefit of U.S. Provisional Application 60/885,700, filedJan. 19, 2007. U.S. patent application Ser. No. 13/536,957 also claimsthe benefit of U.S. Provisional Application 61/503,406, filed Jun. 30,2011; U.S. Provisional Application 61/540,881, filed Sep. 29, 2011; U.S.Provisional Application 61/545,879, filed Oct. 11, 2011; U.S.Provisional Application 61/555,668, filed Nov. 4, 2011; U.S. ProvisionalApplication 61/595,222, filed Feb. 6, 2012; and U.S. ProvisionalApplication 61/645,956, filed May 11, 2012.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to medical devices and methodsfor their fabrication. In particular, the present invention relates tothe fabrication of biodegradable endoprostheses, such as stents, havingenhanced strength and controlled persistence after implantation.

Stents are generally tubular-shaped devices which function to hold openor reinforce a segment of a blood vessel or other body lumen, such as acoronary artery, carotid artery, saphenous vein graft, or femoralartery. They also are suitable to support and hold back a dissectedarterial lining that could occlude the body lumen, to stabilize plaque,or to support bioprosthetic valves. Stents can be formed from variousmaterials, particularly polymeric and/or metallic materials, and may benon-degradable, biodegradable, or be formed from both degradable andnon-degradable components. Stents are typically delivered to the targetarea within the body lumen using a catheter. With balloon-expandablestents, the stent is mounted to a balloon catheter, navigated to theappropriate area, and the stent is expanded by inflating the balloon. Aself-expanding stent is delivered to the target area and released,expanding to the required diameter to treat the disease. Stents may alsoelute various drugs and pharmacological agents.

Of particular interest to the present invention, biodegradable stentsand other endoprostheses are usually formed from polymers which degradeby hydrolysis and other reaction mechanisms in the vascular or otherluminal environment over time.

For these reasons, it would be desirable to provide improvedendoprostheses and methods for their fabrication.

2. Description of the Background Art

Heat annealing and other treatments of filaments and other componentsused in stents are described in U.S. Pat. Nos. 5,980,564, 6,245,103, and6,626,939. Heat treatment of polymeric stent coatings is described inInternational Application No. PCT/US07/81996, which designates theUnited States.

Biodegradable implantable devices and methods of making them are alsodescribed in commonly owned U.S. Provisional Patent Application No.60/668,707, filed on Apr. 5, 2005; U.S. Provisional Patent ApplicationNo. 60/885,700, filed on Jan. 19, 2007; U.S. patent application Ser. No.11/398,363, filed on Apr. 4, 2006; U.S. patent application Ser. No.12/016,077, filed on Jan. 17, 2008; and U.S. patent application Ser. No.12/016,085, filed on Jan. 17, 2008, the entire disclosure of each ofwhich is incorporated herein by reference.

SUMMARY OF THE INVENTION

In an aspect of the invention, improved biodegradable endoprostheses andmethods for their fabrication are provided. The stent prostheses may beformed from one or more amorphous, semi-crystalline, or crystallinebiodegradable polymers. The use of amorphous polymers is preferable insome cases since they can provide relatively short periods ofbiodegradation, usually less than two years, often less than one year,frequently less than nine months, and sometimes shorter than six months,or even shorter.

In some embodiments of the invention, the polymers are modified ortreated to introduce a desired degree of crystallinity. In otherembodiments, introducing crystallinity into the polymer increases thestrength of the polymer so that it is suitable for use as anendoprosthesis and in some cases without substantially lengthening theperiod of biodegradation after implantation. In other embodiments, thepolymeric material is treated to achieve a desired degree ofcrystallinity. In other embodiments, the polymeric material is treatedto control crystallinity.

In an embodiment, treatment comprises a heat treatment of the polymericmaterial or the tubular body preferably at an initial diameter to atemperature above its glass transition temperature of the polymericmaterial and below its melting point for a period ranging from afraction of a second to 7 days. Initial diameter is the diameter of thepolymeric material or the tubular body as-formed, or the diameter beforepatterning, or the diameter after patterning, or the diameter beforecrimping. The polymeric material or the tubular body in one embodimentmay be cooled after heating to a temperature ranging from below ambienttemperature to ambient or above temperature over a period ranging from afraction of a second to 7 days. In a preferred embodiment, the tubularbody or polymeric material initial diameter is approximately 1-1.5 timesthe stent deployment diameter. In one embodiment, the tubular body istreated at diameter below initial diameter, or between initial diameterand crimped diameter. In a further embodiment, the treatment comprisesheating the tubular body to a temperature about or below Tg for a periodranging from a fraction of a second to 7 days. In another embodiment,the heat treatment at the below initial diameter comprises heattreatment about or above Tg and below Tm for a period ranging from afraction of a second to 5 hours, or preferably less than 2 hour, or morepreferably less than 60 minutes, or most preferably less than 15minutes. In another embodiment, the polymeric material or the tubularbody after forming is treated comprising heat at temperature about orless than Tg. In another embodiment, the tubular body after forming andexcluding patterning is treated comprising heat at temperature about orless than Tg. Durations are similar to above ranges. Other suitabletemperatures and times are described herein. In another embodiment, theinitial diameter is 0.9-1.5 times the stent deployment diameter, or thestent nominal diameter. The stent nominal diameter is the labeleddeployment stent diameter. The stent deployment diameter usually is thedeployed diameter of the stent at nominal or bigger diameter. In anotherembodiment, the initial diameter is smaller than the deployed stentdiameter or smaller than the labeled stent deployed diameter.

In some embodiments, a method according to the present invention forfabricating a biodegradable prosthesis comprises providing a tubularbody having an initial diameter, wherein said tubular body is composedat least partially of a substantially amorphous biodegradable polymer,while the diameter remains substantially unchanged; heating the tubularbody to a temperature above a glass transition temperature of thepolymer and below the melting point of the polymer; cooling the tubularbody to increase the crystallinity of the polymer; and patterning thetubular body into a structure capable of radial contraction andexpansion.

In one embodiment, the stent prosthesis after deployment from a crimpedconfiguration to an expanded diameter in physiologic environment furtherexpands to a larger diameter. In another embodiment, the stentprosthesis after deployment from a crimped configuration to an expandeddiameter in physiologic environment further expands to a larger diameterby at least 0.05 mm within 20 minutes. In another embodiment, the stentprosthesis after deployment from a crimped configuration to an expandeddiameter in physiologic environment further expands to a larger diameterby at least 0.1 mm within 20 minutes. In another embodiment, the stentprosthesis after deployment from a crimped configuration to an expandeddiameter in physiologic environment further expands to a larger diametersubstantially apposing the body lumen. The stent prosthesis afterdeployment from a crimped configuration to an expanded diameter inphysiologic environment further expands to a larger diametersubstantially apposing the body lumen within 9 months. In anotherembodiment, the at least some of the struts of the stent prosthesisafter deployment from a crimped configuration to an expanded diameter inphysiologic environment further expands to a larger diametersubstantially apposing the body lumen.

In some embodiments, the optional heat treatment of the one or morebiodegradable polymeric materials, or the tubular body, the stentmaterial, or the stent may occur at a temperature below T_(g), or atabout T_(g), or at greater than T_(g) of the one or more biodegradablepolymeric materials. In some embodiments, the optional heating may takeplace at a temperature within 2° C., or within 4° C., or within 6° C.,or within 8° C., or within 10° C., or within 12° C., or within 14° C.,or within 16° C., or within 18° C., or within 20° C. of T_(g) of the oneor more biodegradable polymeric materials (where “within” may be aboveor below the T_(g)). In some embodiments the optional treating, such asheating, may take place for at least about 1×10⁻¹² seconds (s), or atleast about 1×10⁻⁹ s, or at least about 1×10⁻⁶ s, or at least about1×10⁻³ s, or at least about 1×10⁻² s, or at least about 0.1 s, or atleast about 1 s, or at least about 10 s, or at least about 1 minute(min), or at least about 10 min, or at least about 1 hour (h) or atleast about 10 h, or at least about 1 day, or at least about 5 days, orat least about 10 days, or at least about 1 month, or at least about 2months, or at least about 3 months, or at least about 4 months, or atleast about 5 months, or at least about 6 months, or at least about 1year. In some cases, the treating, such as heating, may take place forabout 1 min to about 10 min, or about 3 min to about 10 min, or about 5min to about 10 min, or about 3 min to about 10 min, or about 30 secondsto about 24 hours.

In some embodiments, the polymers' crystallinity after modification ortreatment is increased by at least 10% of the original crystallinity ofthe polymer material, preferably by at least 20% of the originalcrystallinity of the polymer material, preferably by at least 50% of theoriginal crystallinity of the polymer material, and more preferably byat least 100% of the original crystallinity of the polymer material.

In other embodiments, the crystallinity of the polymeric material aftermodification is decreased by at least 10% of the original crystallinityof the polymer material before modification, preferably by at least 20%of the original crystallinity of the polymer material, preferably by atleast 50% of the original crystallinity of the polymer material, andmore preferably by at least 100% of the original crystallinity of thepolymer material, and more preferably by at least 1000% of the originalcrystallinity of the polymer material. In other embodiments, treatmentor modification of the polymeric material has crystallinity that issubstantially the same after treatment and before treatment of thepolymeric material.

In preferred embodiments, polymer materials will have a crystallinity inthe range from 10% to 20% after modification as described herein below.In yet other preferred embodiments, polymer materials will have acrystallinity in the range from 1 to 10%, or 10% to 30% aftermodification. In yet other preferred embodiments, polymer materials willhave a crystallinity between 1% and 35% after modification. In yet otherpreferred embodiments, polymer materials will have a crystallinitybetween 1% and 40% after modification. As used herein and as known toskilled in the art, “crystallinity” refers to a degree of structuralorder or perfection within a polymer matrix as known to someone skilledin the art and methods to measure crystallinity as well such asdifferential scanning calorimetry.

In some embodiments, the one or more materials comprising the body, orthe stent, or the tubular body may have a controlled crystallinity. Insome embodiments, the crystallinity is less than 50%, or less than 40%,or less than 35%, or less than 30%, or less than 25%, or less than 20%,or less than 15%, or less than 10%, or less than 5%. In someembodiments, the one or more materials comprising the body, or thestent, or the tubular body, or the polymeric material may have acrystallinity of about 0% or greater than 0%, or greater than 5%, orgreater than 10%, or greater than about 15%, or greater than about 20%,or greater than about 25%, or greater than about 30%, or greater thanabout 35%, or greater than 40%, or greater than 50%. In someembodiments, the one or more materials comprising the body, or thestent, or the tubular body may have a crystallinity of about 0% to lessthan 60%, or about 0 to less than 55%, or about 0 to less than 50%, orabout 0 to less than 40%, or about 0% to less than 35%, or about 0% toless than 30%, or about 0% to less than 25%, or about 0% to less than20%, or about 0% to less than 15%, or about 0% to less than 10%, orabout 0% to less than 5%. In some embodiments, the one or more materialscomprising the body, or the stent, or the tubular body or polymericmaterial may have a crystallinity of about 5% to about 60%, or about 5%to about 55%, or about 5% to about 50%, or about 5% to about 40%, orabout 5% to about 45%, or about 5% to about 30%, or about 10% to about25%, or about 15% to about 20%.

In some embodiments, the polymer or polymeric material after treatmentis amorphous, in other embodiments the polymer or polymeric materialafter treatment is semi-crystalline, yet in other embodiments thepolymer or polymeric material after treatment is crystalline. In apreferred embodiment, the polymeric material prior to a treatment isamorphous. In other embodiments, the polymeric material prior to atreatment is semi-crystalline. In a further embodiment, the polymericmaterial prior to a treatment is crystalline.

Crystallinity can be measured by differential scanning calorimetry(Reading, M. et al, Measurement of crystallinity in polymers usingmodulated temperature differential scanning calorimetry, in MaterialCharacterization by Dynamic and Modulated Thermal Analytical Techniques,ASTM STP 1402, Riga, A. T. et al. Ed, (2001) pp. 17-31.

In another aspect of the invention, methods for fabricatingbiodegradable prostheses are provided. The preferred methods compriseproviding a tubular body having an initial diameter as-formed, or beforepatterning, or after patterning, where the tubular body comprises abiodegradable polymeric material. In one embodiment, the polymericmaterial comprises one or more polymers, or one or more co-polymers, ora combination thereof. In another embodiment, the polymeric materialcomprises one or more polymers, or one or more co-polymers, or one ormore monomers, or a combination thereof. The polymeric material or thetubular body is treated to control crystallinity preferably to between1% and 50%, or more preferably to between 1% and 35%. In one embodimentthe polymeric material or the tubular body treatment comprises a heattreatment preferably at substantially the initial diameter, preferablywhen the initial diameter is 1-1.5 times the stent deployment diameter,to a temperature above glass transition temperature of the polymericmaterial and below its melting point for a period ranging from afraction of a second to 7 days. The polymeric material or the tubularbody in one embodiment may be cooled after heating to a temperatureranging from below ambient temperature to ambient or above temperatureover a period ranging from a fraction of a second to 7 days. In apreferred embodiment, the polymeric material or the tubular body initialdiameter is approximately 1-1.5 times the stent deployment diameter orstent nominal deployment diameter, or stent labeled deployment diameter.In another preferred embodiment, the initial diameter is approximately0.9-1.5 times the stent deployment diameter or stent nominal deploymentdiameter, or stent labeled deployment diameter. In another embodiment,the initial diameter is smaller than the stent deployment diameter orstent nominal deployment diameter, or stent labeled deployment diameter.The stent deployment diameter in a preferred embodiment is typically thediameter of the stent deployed to approximately nominal or labeled stentdiameter but can also be the deployed diameter above the stent nominalor labeled diameter. Stent nominal deployed diameter can be accomplishedin one example by inflating the deploying balloon to nominal or labeleddiameter to deploy the stent to nominal or labeled diameter. In apreferred embodiment, the polymeric material or the tubular body ispatterned at substantially the initial diameter and is crimpedsubsequently to a crimped diameter that is smaller than the initialdiameter. In one embodiment, the polymeric material or the tubular bodyis treated at diameter between initial diameter and crimped diameter. Ina further embodiment, the treatment comprises heating the tubular bodyto a temperature about or below Tg for a period ranging from a fractionof a second to 7 days. In another embodiment, the heat treatment at thebelow initial diameter comprises heat treatment about or above Tg andbelow Tm for a period ranging from a fraction of a second to 5 hours, orpreferably less than 2 hour, or most preferably less than 60 minutes, ormost preferably less than 15 minutes. The patterned stent in oneembodiment is crimped in one or more steps and fitted onto a deliverysystem or crimped onto the delivery system at a diameter that is lessthan the initial diameter. In another embodiment, the crimped diameteris less than 3 mm, in another embodiment, the crimped diameter is lessthan 2.5 mm, in another embodiment, the crimped diameter is less than2.0 mm in a third embodiment, the crimped diameter is less than 1.5 mm,in a fourth embodiment, the crimped diameter is less than 1 mm, in afifth embodiment, the crimped diameter is less than 0.8 mm. In apreferred embodiment, the stent is capable to expand from the crimpeddiameter to a deployed diameter preferably at about body temperature (inwater or dry) and have sufficient strength to support a body lumen. In afurther preferred embodiment, the stent is capable to expand from thecrimped diameter to a deployed diameter at about body temperature (inaqueous or water or dry) without fracture and have sufficient strengthto support a body lumen. In a further preferred embodiment, the stent iscapable to crimp from an expanded diameter, wherein the expandeddiameter is larger than the crimped diameter, and expand from thecrimped diameter to a deployed diameter at about body temperature (inaqueous or water or dry) without fracture and have sufficient strengthto support a body lumen.

In some embodiments, sufficient radial strength to support a body lumenis maintained for at least 1 month, or for at least 2 months, for atleast 3 months. In some embodiments, the diameter of the scaffoldincreases after expansion to nominal diameter or between nominal and 1.1times nominal diameter by 0.1 mm to 0.5 mm between 5 minutes afterdeployment to an expanded diameter and 1 hour. In other embodiments, thediameter of the scaffold did not substantially decrease over time. Instill other embodiments, the diameter of the scaffold did notsubstantially increase over time.

In some embodiments, an expandable stent comprising a biodegradablepolymeric material having an initial configuration is provided. Theexpandable stent at body temperature can be self-expandable from acrimped configuration and further expandable to a second largerconfiguration. In further embodiments, the polymeric material has beentreated to control one or more of crystallinity, Tg, or molecularweight. In some embodiments, the Tg ranges from about 20° C. to about50° C. In some embodiments, the second configuration is a deployedconfiguration. In some embodiments, the stent expands to the first andsecond configurations without fracture and has sufficient strength tosupport a body lumen. In some embodiments, the first expandedconfiguration has a transverse dimension of at least 0.35 times, or atleast 0.45 times, or at least 0.55 times, or at least 0.55 times, or atleast 0.7 times, or at least 0.8 times, or at least 1 times thetransverse dimension of the initial configuration. In some embodiments,the stent expands to the first expanded configuration within a period of24 hours, or 12 hours, or 4 hours, or 2 hours, or 1 hour, or 30 minutes,or 5 minutes or 30 seconds. In some embodiments, the stent is balloonexpandable to the second expanded configuration without fracture andwith sufficient strength to support a body lumen.

In some embodiments, an expandable stent comprising a biodegradablepolymeric material having an initial configuration is provided. Theexpandable stent at body temperature can be expandable from a crimpedconfiguration to a first expanded configuration and self expandable to asecond larger configuration. In further embodiments, the polymericmaterial is treated to control one or more of crystallinity, Tg, ormolecular weight. In some embodiments, the expandable stent comprises asubstantially continuous tubular body. In some embodiments, the stentexpands to the first configuration without fracture and has sufficientstrength to support a body lumen. In some embodiments, the stent has anominal expanded configuration with a transverse dimension and the firstexpanded configuration has a transverse dimension that is at least 1times the transverse dimension of the transverse dimension of thenominal expanded configuration. In some embodiments, the first expandedconfiguration is a deployed configuration. In some embodiments, thestent has a nominal expanded configuration with a transverse dimensionand the first expanded configuration has a transverse dimension that is1 time, or 1.1 times, or 1.2 times, or 1.3 times, or 1.35 times, or 1.4times, or 1.45 times, or 1.5 times the transverse dimension of thetransverse dimension of the nominal expanded configuration.

Fabricating a biodegradable stent can be accomplished through a varietyof ways. In a preferred embodiment, the biodegradable stent isfabricated by forming a tubular body using extrusion, molding such asinjection molding, dipping, spraying such as spraying a tube or mandrel,printing such as 3D printing. The tubular body in a preferred embodimentis formed first and then patterned into a structure capable of radialexpansion from a crimped configuration preferably at body temperature.The tubular body in another preferred embodiment is formed first andthen patterned into a structure capable of radial expansion from acrimped configuration preferably at body temperature and preferablywithout fracture. The tubular body in another preferred embodiment isformed first and then patterned into a structure capable of beingcrimped from an expanded configuration to a crimped diameter (attemperature about Tg or less than Tg), and at body temperature capableto be expanded from the crimped configuration preferably withoutfracture. In another preferred embodiment the polymeric material ispatterned first and then forms a tubular body/stent capable of radialexpansion at body temperature and/or capable to be crimped preferably attemperature about Tg or less than Tg. In another preferred embodiment,the biodegradable stent is fabricated from a sheet (such as a flatsheet) joined at ends (such as opposite ends) to form a tubular bodycapable of radial expansion preferably at body temperature and/orcapable to be crimped preferably at temperature about Tg or less thanTg, and patterned before and/or after joining. Joining sheet ends can beaccomplished by a variety of methods such as adhesive, ultrasound,welding, melting the ends, chemical means, or treatment such as heating.The tubular body formed from a sheet can be further treated to controlcrystallinity and Tg as described in this patent application. Thetubular body formed form the sheet has an initial diameter, preferably1-1.5 times the stent deployed diameter. In other preferred embodiment,the biodegradable stent is fabricated from weaving or braiding polymericmaterial fibers into a tubular body structure capable of expansion atbody temperature and/or capable to be crimped at temperature preferablyabout Tg or less than Tg. Preferably, weaving or braiding of thepolymeric material such as fibers into the initial tubular configurationwhich is capable of radial expansion at body temperature and/or capableof being crimped from an expanded diameter preferably at temperatureabout Tg or less than Tg (in aqueous or dry environment) wherein theinitial diameter is preferably 1-1.5 times the stent deployed diameter(or the stent nominal diameter, or the stent labeled diameter) andpreferably treated at the initial tubular diameter, to achievecontrolled crystallinity preferably between 0 and 45%, or morepreferably between 0 and 35% and a Tg greater than 37° C. and less than50° C., or more preferably greater than 37° C. and less than 45° C.) andthe stent is capable to expand from a crimped configuration to anexpanded configuration/diameter at body temperature and has sufficientstrength to support a body lumen, and preferably without fracture. Inanother preferred embodiment, the stent is capable to be crimped (attemperature preferably about Tg or below Tg), and expand from a crimpedconfiguration to an expanded configuration/diameter at body temperatureand has sufficient strength to support a body lumen, and preferablywithout fracture.

In another preferred embodiment, the biodegradable stent is formed usinginjection molding wherein the polymeric material is loaded inside a moldand the mold is treated once or more to control crystallinity preferablyto between 1% and 55% (preferably between 1% and 35%) and treated tocontrol Tg preferably to greater than 37° C. and less than 50° C. (or inanother preferred embodiment control Tg to greater than 20° C. and lessthan 50° C.), or as described within this patent application. The formedpatterned tube/stent has an initial diameter, preferably 1-1.5 times thestent deployed diameter, and the treatment can take place before, and/orduring, and/or after the molding process and the stent capable toradially expand preferably at body temperature (dry or in aqueousenvironment). The stent in another embodiment is capable to be expandedfrom a crimped configuration (which is smaller than the expandeddiameter) to an expanded diameter at body temperature and havesufficient strength to support a body lumen, and preferably withoutfracture. The stent in another embodiment is capable to be crimped froman expanded diameter to a crimped diameter (at temperature preferablyabout Tg or less than Tg), and expanded from the crimped configurationto an expanded diameter at body temperature and have sufficient strengthto support a body lumen, and preferably without fracture. In anotherpreferred embodiment, the biodegradable stent can be fabricated usingprinting such as 3-D printing wherein the polymeric material is loadedonto the printer and treated to form a patterned tubularbody/structure/stent wherein it has an initial diameter, preferably1-1.5 times the stent deployed diameter, and is treated to controlcrystallinity and Tg as described within this patent application, andthe stent is capable to radially expand at body temperature. The stentin another embodiment is capable to expand from a crimped configurationto an expanded diameter at body temperature and has sufficient strengthto support a body lumen, and preferably without fracture. The stent inanother preferred embodiment is capable to be crimped from an expandeddiameter to a crimped configuration (at temperature preferably about Tgor less than Tg), and expand from the crimped configuration to anexpanded diameter at body temperature and has sufficient strength tosupport a body lumen, and preferably without fracture. Although thepreferred embodiment when crimping the stent is at temperature about Tgor less than Tg, crimping the stent can be accomplished at temperatureabove Tg or within 20° C. above Tg. Although treatment by heat typicallyranges from below Tg to below Tm, in some other cases treatment of thepolymeric material can be about Tm or above for example when the stentis formed by printing or injection molding. A preferred formationprocess comprises forming a tube using spraying a polymer or polymericmaterial comprising one or more polymer, co-polymer- or monomerdissolved in at least one solvent onto a cylindrical mandrel or otherstructure when the stent prosthesis desired shape is non cylindricalsuch as oblong shape or other shapes. When the stent prosthesis is notcylindrical, a dimension of the stent may be referred to as “transversedimension” instead of diameter. Optionally, additives, such asstrength-enhancing materials, drugs, or the like, may be dissolved inthe solvent or other solvents together with the polymer or polymericmaterial so that the materials are integrally or monolithically formedwith the endoprosthesis tube. Alternatively, methods according toembodiments of the invention may rely on obtaining a pre-formed polymertube from a supplier or other outside source.

In some embodiments, the polymeric tubular body is usually formed as asubstantially continuous cylinder free from holes or otherdiscontinuities. In another embodiment, the tubular body has aforaminous wall. In a third embodiment, the tubular body is formed froma continuous tube. In a fourth embodiment, the tubular body comprises aplurality of fibers woven into an expanded diameter, preferably theinitial tubular configuration with a diameter preferably of 1-1.5 timesthe stent deployed diameter and preferably treated at the initialtubular diameter. The polymeric material or the tubular body or deployedstent typically has an outside or inner diameter in the range from 2 mmto 25 mm, preferably 3 mm to 10 mm, or 3.5 mm to 10 mm, and a thicknesspreferably in the range from 0.01 mm to 0.5 mm, and may be cut intolengths suitable for individual endoprostheses, typically in the rangefrom 5 mm to 40 mm but can also range from 1 mm to 150 cm.

In an embodiment, the tubular body may be patterned into a suitableendoprosthesis structure, typically by laser cutting or otherconventional processes such as milling, chemical etching, stamping,photolithography, etc. In other embodiments, the stent prosthesis isformed by 3D printing which patterns the tubular body/stent as it isbeing formed and optionally treated to control crystallinity and Tg tofacilitate a stent capable to radially expand at body temperature andsupport a body lumen and preferably without fracture. In anotherembodiment, the tubular body comprises a plurality of fibers woven intothe initial tubular configuration with a diameter preferably of 1-1.5times the stent deployed diameter and preferably treated at the initialtubular diameter. In another embodiment, the stent tubular body isformed from a sheet joined at opposite ends and patterned either beforeor after joining.

In some embodiments, as described herein, a biodegradable endoprosthesis(e.g., a stent) is formed from a polymeric tube, wherein the tube is asubstantially continuous cylinder. In some cases, the substantiallycontinuous cylinder may be substantially free from holes, gaps, voids orother discontinuities. In other embodiments, the tube may besubstantially continues yet include some holes, gaps, voids, or otherdiscontinuities. The tubular body may have an outside diameter in therange from about 2 mm to 10 mm, or about 3 mm to about 9 mm, or about 4mm to about 8 mm, or about 5 mm to about 7 mm. The tubular body may havea thickness in the range from 0.01 mm to 0.5 mm, or about 0.05 mm toabout 0.4 mm, or about 0.1 mm to about 0.3 mm.

In certain embodiments, the tubular body or polymeric material, or thestent has an initial diameter. In one preferred embodiment, the initialdiameter is 1-1.5 times the stent deployed diameter. In anotherpreferred embodiment, the initial diameter is 0.9-1.5 times the stentdeployed diameter. In a further embodiment, the initial diameter is lessthan the stent deployed diameter. The initial diameter can be theas-formed diameter, or the diameter before patterning, or the diameterafter patterning, or the diameter before crimping. In one embodiment, anendoprosthesis (e.g., a stent) is patterned by laser cutting or othermethod from a polymeric tube that has a (e.g., inner or outer) diametersubstantially equal to or smaller than deployed (e.g., inner or outer)diameter of the endoprosthesis. In other embodiments, an endoprosthesis(e.g., a stent) is patterned from a polymeric tube that has a (e.g.,inner or outer) diameter, either when the tube is formed or after thetube is radially expanded to a second larger diameter, larger thandeployed (e.g., inner or outer) diameter of the endoprosthesis.Patterning a stent from a polymeric tube having a (e.g., inner or outer)diameter larger than deployed (e.g., inner or outer) diameter of thestent can impart advantageous characteristics to the stent, such asreducing radially inward recoil of the stent after deployment and/orimproved strength. In certain embodiments, a stent is patterned from apolymeric tube having a (e.g., inner or outer) diameter about 0.85,0.90, 1.0, 1.05 to about 1.5 times, or about 1.1 to about 1.5 times, orabout 1.1 to about 1.3 times, or about 1.15 to about 1.25 times,smaller, same, or larger than an intended deployed (e.g., inner orouter) diameter of the stent. In an embodiment, the stent is patternedfrom a polymeric tube having a (e.g., inner or outer) diameter about 1.1to about 1.3 times larger than an intended deployed (e.g., inner)diameter of the stent. For example, a stent having a deployed (e.g.,inner or outer) diameter of about 2.5, 3 or 3.5 mm can be patterned froma tube having a (e.g., inner or outer) diameter of about 2.75, 3.3 or3.85 mm (1.1 times larger), or about 3.25, 3.9 or 4.55 mm (1.3 timeslarger), or some other (e.g., inner or outer) diameter larger than thedeployed (e.g., inner or outer) diameter of the stent. In preferredembodiments, the initial diameter of the formed tube is larger than thecrimped diameter (e.g., crimped diameter on a delivery system) of thestent prosthesis wherein the tubular body is expanded to a second largerdiameter than the initial diameter before patterning or before crimpingto the crimped diameter; or wherein the tubular body remainssubstantially the same diameter before patterning or before crimping toa crimped diameter; or wherein the tubular body is crimped to a smallerdiameter than the initial formed diameter before patterning or afterpatterning. In another embodiment, the initial diameter of the formedtube is smaller than the crimped diameter of the stent prosthesiswherein the tubular body is expanded to a second larger diameter thanthe initial diameter before patterning or before crimping; or whereinthe tubular body remains substantially the same diameter beforepatterning or before crimping; or wherein the tubular body is crimped toa smaller diameter than the crimped diameter of the stent prosthesisbefore patterning or after patterning. In another embodiment, theinitial diameter of the formed tubular body is greater than 0.015inches, or greater than 0.050 inches, or greater than 0.092 inches, orgreater than 0.120 inches, or greater than 0.150 inches, in theas-formed diameter, or before patterning diameter, or after patterningdiameter, or before crimping diameter. Stent prosthesis intendeddeployment diameter is the diameter of the labeled or nominal or higherof the delivery system or balloon catheter, or higher. For example whena stent prosthesis is crimped onto a balloon labeled 3.0 mm diameter(e.g., deployed nominal diameter), the stent prosthesis' deployeddiameter or intended deployment diameter is 3.0 mm or higher. Similarly,self expandable stent crimped onto a delivery system is labeled acertain deployment diameter. In a preferred embodiment, a stentprosthesis or tubular body or polymeric material has initial diameter(or initial transverse dimension), preferably 1-1.5 times deployeddiameter (deployed transverse dimension) or deployed nominal diameter(e.g., deployed nominal transverse dimension), where in the initialdiameter (or initial transverse dimension) is as-formed diameter (ortransverse dimension), before patterning diameter (or transversedimension), or after patterning diameter (or transverse dimension), orbefore crimping diameter (or transverse dimension), and wherein theinitial diameter (or initial transverse dimension) is greater thancrimped diameter (or crimped transverse dimension).

In a preferred embodiment, a stent or tubular body first self-expands byat least 0.35 of initial diameter or transverse dimension, and thenexpands to second larger diameter or transverse dimension, which may bethe deployed diameter or transverse dimension, preferably by balloonexpansion. In a further preferred embodiment, the stent or tubular bodymay expand to 1.0 times or more, or 1.1 times or more, or 1.2 times ormore, or 1.3 times or more, or 1.4 times or more, or 1.5 times or morethe deployed diameter or nominal diameter (or transverse dimension) atbody temperature, without fracturing. In a further preferred embodiment,the stent or tubular body or polymeric material is crimped from anexpanded diameter to a crimped configuration, and at body temperatureexpands to 1.0 times or more, or 1.1 times or more, or 1.2 times ormore, or 1.3 times or more, or 1.4 times or more, or 1.5 times or morethe deployed diameter or nominal diameter (or transverse dimension),without fracturing. In a further preferred embodiment, the stent ortubular body is crimped from an expanded diameter to a crimpedconfiguration wherein the ratio of expanded diameter to crimpedconfiguration is at least 1.5, and at body temperature the stent expandsto 1.0 times or more, or 1.1 times or more, or 1.2 times or more, or 1.3times or more, or 1.4 times or more, or 1.5 times or more the deployeddiameter or nominal diameter (or transverse dimension), withoutfracturing. In a further preferred embodiment, the stent or tubular bodyis crimped from an expanded diameter to a crimped configuration whereinthe ratio of expanded diameter to crimped configuration is at least 2,and at body temperature the stent expands to 1.0 times or more, or 1.1times or more, or 1.2 times or more, or 1.3 times or more, or 1.4 timesor more, or 1.5 times or more the deployed diameter or nominal diameter(or transverse dimension), without fracturing. In a further preferredembodiment, the stent or tubular body is crimped from an expandeddiameter to a crimped configuration wherein the ratio of expandeddiameter to crimped configuration is at least 2.5, and at bodytemperature the stent expands to 1.0 times or more, or 1.1 times ormore, or 1.2 times or more, or 1.3 times or more, or 1.4 times or more,or 1.5 times or more the deployed diameter or nominal diameter (ortransverse dimension), without fracturing. In a further preferredembodiment, the stent or tubular body is crimped from an expandeddiameter to a crimped configuration wherein the ratio of expandeddiameter to crimped configuration is at least 3, or at least 4, or atleast 5, or at least 6, or at least 7, and at body temperature the stentexpands to 1.0 times or more, or 1.1 times or more, or 1.2 times ormore, or 1.3 times or more, or 1.4 times or more, or 1.5 times or morethe deployed diameter or nominal diameter (or transverse dimension),without fracturing. In a further preferred embodiment, the stent ortubular body is crimped from an expanded diameter to a crimpedconfiguration wherein the ratio of expanded diameter to crimpedconfiguration is at least 2, or at least 2.5, or at least 3, or at least3.5, or at least 4, wherein the stent at body temperature is expandablefrom the crimped configuration to the deployed configuration withoutfracture, wherein the deployed configuration is the nominal or higherdeployment diameter. In another preferred embodiment, the stent isballoon expanded to its deployed diameter (or transverse dimension)first and then expands, preferably self expands, to a second largerdiameter (or transverse dimension) by about 0.1 mm or more, or about 0.2mm or more, or about 0.3 mm or more, or about 0.4 mm or more, or about0.5 mm or more, without fracture. In a further preferred embodiment, theballoon expandable stent or tubular body or polymeric material expandsto 1.0 times or more, or 1.1 times or more, or 1.2 times or more, or 1.3times or more, or 1.4 times or more, or 1.5 times or more the deployeddiameter or nominal diameter (or transverse dimension) at bodytemperature, without fracturing. In a further preferred embodiment, thestent or tubular body is crimped from an expanded diameter to a crimpedconfiguration, and at body temperature is balloon expandable to 1.0times or more, or 1.1 times or more, or 1.2 times or more, or 1.3 timesor more, or 1.4 times or more, or 1.5 times or more the deployeddiameter or nominal diameter (or transverse dimension), withoutfracturing. In a further preferred embodiment, the stent or tubular bodyis crimped from an expanded diameter to a crimped configuration whereinthe ratio of expanded diameter to crimped configuration is at least 1.5,and at body temperature the balloon expandable stent expands to 1.0times or more, or 1.1 times or more, or 1.2 times or more, or 1.3 timesor more, or 1.4 times or more, or 1.5 times or more the deployeddiameter or nominal diameter (or transverse dimension), withoutfracturing.

An endoprosthesis (e.g., a stent or a stent delivery system) and/or thepolymeric article/material (e.g., a polymeric tube) from which it isformed can be exposed to ionizing radiation such as electron beam orgamma radiation or to ethylene oxide gas (e.g., for purposes ofsterilization and/or treatment) as described herein. Such modificationor treatment in that it can, e.g., control crystallinity (e.g., degreeof crystallinity), control Tg, control molecular weight, control monomercontent, and/or enhance the strength of the material (e.g., polymericmaterial) comprising the polymeric article or the endoprosthesis. Insome embodiments, the polymeric article and/or the endoprosthesis areexposed to a single dose or multiple doses of e-beam or gamma radiationtotaling about 5 or 10 kGy to about 50 kGy, or about 20 kGy to about 40kGy of radiation, e.g., a single dose of 30 kGy or multiple smallerdoses (e.g., 3×10 kGy doses)], where the polymeric article and/or theendoprosthesis are optionally (cooled to low temperature (e.g., about−10° C. to about −30° C., or about −20° C. to less than ambienttemperature) for a period of time (e.g., at least about 1 minute, 20, 30or 40 minutes) or optionally treated at about ambient temperature) priorto exposure to the single dose or to each of the multiple doses ofradiation. In certain embodiments, the polymeric article and/or theendoprosthesis are exposed to a single dose or multiple doses of e-beamor gamma radiation totaling about 10 kGy to about 50 kGy, or about 30kGy. A polymeric article and/or an endoprosthesis that have been exposedto ionizing radiation or ethylene oxide gas can also undergo one or moreother modification treatments (e.g., heating or annealing and/orcooling) described herein.

In some embodiments, the tubular body or polymeric material or stent maybe formed from at least one polymer having desired degradationcharacteristics where the polymer may be modified to have the desiredcrystallinity, Tg, recoil, strength, shortening, expansioncharacteristics, crimping characteristics, crystallinity, Tg, molecularweight, and/or other characteristics in accordance with the methods ofthe present invention. Polymers include one or more polymers,copolymers, blends, and combination thereof of: Lactides, Glycolides,Caprolactone, Lactides and Glycolides, Lactides and Caprolactones:examples poly-DL-Lactide, polylactide-co-glycolactide;polylactide-co-polycaprolactone, poly (L-lactide-co-trimethylenecarbonate), polylactide-co-caprolactone, polytrimethylene carbonate andcopolymers; polyhydroxybutyrate and copolymers; polyhydroxyvalerate andcopolymers, poly orthoesters and copolymers, poly anhydrides andcopolymers, polyiminocarbonates and copolymers and the like. Aparticularly preferred polymer comprises a copolymer of L-lactide andglycolide, preferably with a weight ratio of 85% L-lactide to 15%glycolide.

In one aspect of the invention, the tubular body or polymeric materialor stent material comprises a degradable polymeric material wherein thepolymeric material comprises one or more polymers; or one or moreco-polymers; or one or more blends of monomers, polymers or copolymers;and combination thereof. In another embodiment, the polymeric materialcomprises one or more polymer or one or more co-polymer. Additionally,at least one monomer, polymer, or co-polymer of similar material (to theone or more polymer or the one or more co-polymer) is blended with thepolymeric material. In another embodiment, a different monomer,co-polymer, or polymer is blended with (the one or more polymer or theone or more co-polymer) the polymeric material. In a preferredembodiment, a biodegradable stent comprising a polymeric materialcomprising a copolymer of lactide and caprolactone in the ratio byweight ranging from 80-99% lactide to 1-20% caprolactone; wherein thepolymeric material further comprises a monomer or polymer includingcopolymer of one or more of the following: lactide, glycolide, lactideglycolide, caprolactone, and lactide caprolactone; wherein the one ormore monomer or polymer total amount is 1 to 100 micrograms permilligram of polymeric material, preferably 5 to 75 micrograms permilligram of polymeric material, more preferably 10 to 50 micrograms permilligrams of polymeric material; wherein the stent is capable to becrimped from an expanded configuration to a smaller crimpedconfiguration, and at body temperature expanded to a deployedconfiguration, and having sufficient strength to support a body lumen,and without fracture of the stent. In another preferred embodiment, abiodegradable stent comprising a polymeric material comprising acopolymer of lactide and caprolactone in the ratio by weight rangingfrom 80-99% lactide to 1-20% glycolide; wherein the polymeric materialfurther comprises a monomer or polymer including copolymer of one ormore of the following: lactide, glycolide, lactide glycolide,caprolactone, and lactide caprolactone; wherein the one or more monomeror polymer total amount is 1 to 100 micrograms per milligram ofpolymeric material, preferably 5 to 75 micrograms per milligram ofpolymeric material, more preferably 10 to 50 micrograms per milligramsof polymeric material; wherein the stent is capable to be crimped froman expanded configuration to a smaller crimped configuration, and atbody temperature expanded to a deployed configuration, and havingsufficient strength to support a body lumen, and without fracture. In afurther embodiment, the one or more monomer and/or polymer does notsubstantially change the crystallinity of the polymeric material. In afurther embodiment, the one or more monomer and/or polymer changes(increases or decreases) the crystallinity of the polymeric material by5% to 150%, preferably by 10% to 75%, more preferably by 10% to 50%. Ina further embodiment, the one or more monomer and/or polymer controlsthe crystallinity of the polymeric material to between 1% and 55%,preferably between 1% and 35%. In a further embodiment, the one or moremonomer and/or polymer does not change the crystallinity of thepolymeric material from being between 1% and 55%. In a furtherembodiment, the one or more monomer and/or polymer does notsubstantially change the Tg of the polymeric material. In a furtherembodiment, the one or more monomer and/or polymer changes (increases ordecreases) the Tg temperature of the polymeric material by 1 C to 15 C,preferably 1° C. to 10° C., more preferably by 1° C. to 5° C. In yet afurther embodiment, the one or more monomer and/or polymer controls theTg temperature of the polymeric material to between 20° C. and 55° C.,preferably to between 35° C. and 50° C., more preferably to between 37°C. and 50° C., most preferably between 37° C. and 45° C.

The polymeric material/article and/or the tubular body and/or theprosthesis or device can undergo any of a variety of modification ortreatments (e.g., longitudinal extension, longitudinal shrinkage, radialexpansion, heating, cooling, quenching, pressurizing, exposure to orhumidity, vacuuming, exposure or incorporation or removal of solvents,incorporation of additive, removal of additives, incorporation of orremoval of impurities, exposure to radiation, incorporation or exposureor pressurization by gases such as carbon dioxide, or a combinationthereof) designed to control or enhance characteristics (e.g.,crystallinity, Tg, molecular weight, strength, toughness anddegradation, recoil, shortening, expansion) of the article, the tubularbody, the polymeric material, and/or the prosthesis or device. Thebiodegradable implantable device formed from a polymeric article made byspraying, extrusion, dipping, molding, 3D printing, and the like, canhave any features of a biodegradable implantable device comprising abody comprising a biodegradable polymer (including homopolymer orcopolymer) described herein. In some embodiments, modification ortreatment may include heating, and/or pressurizing. In one preferredembodiment, the polymeric material is treated wherein the treatmentcomprises incorporation of solvents wherein the one or more solventamounts in the polymeric material or the stent after treatment rangesfrom 0.001% to 10% by weight, preferably ranges from 0.1% to 5% byweight, more preferably ranges from 0.1% to 3% by weight. In onepreferred embodiment, the polymeric material is treated wherein thetreatment comprises incorporation of solvents wherein the one or moresolvent amounts in the polymeric material or the stent after treatmentranges from 0.001% to 10% by weight, preferably ranges from 0.1% to 3%by weight, more preferably ranges from 0.1% to 2% by weight and whereinthe stent at body temperature is capable to expand from a crimpedconfiguration to a deployed diameter without fracture and havesufficient strength to support a body lumen. In one preferredembodiment, the polymeric material is treated wherein the treatmentcomprises incorporation of solvents wherein the one or more solventamounts in the polymeric material or the stent after treatment rangesfrom 0.001% to 10% by weight, preferably ranges from 0.1% to 3% byweight, more preferably ranges from 0.1% to 2% by weight and wherein theone or more solvent substantially does not dissolve the stent(preferably does not dissolve the stent) and wherein the stent at bodytemperature is capable to expand from a crimped configuration to adeployed diameter without fracture and have sufficient strength tosupport a body lumen. In one preferred embodiment, the polymericmaterial is treated wherein the treatment comprises incorporation ofsolvents wherein the one or more solvent amounts in the polymericmaterial or the stent after treatment ranges from 0.001% to 10% byweight, preferably ranges from 0.1% to 3% by weight, more preferablyranges from 0.1% to 2% by weight and wherein the one or more solventpreferably substantially does not dissolve the stent (preferably doesnot dissolve the stent) and wherein the one or more solventsubstantially remains in the stent in the ranges described above beforedeployment of the stent) wherein the stent at body temperature iscapable to expand from a crimped configuration to a deployed diameterwithout fracture and have sufficient strength to support a body lumen.Examples of solvents include DCM, Chloroform to name some. Incorporationof solvents for example by spraying as described in the application.Solvents that can be used for example are ones that dissolves thepolymeric material when used in sufficient quantities or solvents thatdoes not dissolve the polymeric material. Preferred solvents aresolvents that are retained in the polymeric material or stent afterincorporation, or after treatment, or before deployment in the rangesdescribed above. Preferred Tg ranges from 20° C. to 50° C., morepreferred from greater than 37° C. to less than 50° C. Preferredcrystallinity ranges from 1% to 60%, preferably from 1% to 55%, morepreferably from 1% to 45%, most preferably from 1% to 35%. The polymericmaterial preferably has an initial diameter, preferably 1-1.5 times thedeployment diameter of the stent. In a preferred embodiment, the stentis capable of being crimped from an expanded diameter to a crimpeddiameter, and at body temperature is capable to expand from a crimpedconfiguration to a deployed diameter without fracture and havesufficient strength to support a body lumen. Examples of polymericmaterial are materials comprising lactide, lactide and glycolide, orlactides and caprolactones, or a combination thereof.

In one preferred embodiment, the polymeric material is treated whereinthe treatment comprises inducing or incorporation of monomers orpolymers including co-polymers wherein the one or more monomers orpolymers amounts in the polymeric material or the stent after treatmentranges from 0.001% to 10% by weight, preferably ranges from 0.1% to 5%by weight, more preferably ranges from 0.1% to 3% by weight. In onepreferred embodiment, the polymeric material is treated wherein thetreatment comprises inducing or incorporation of monomers or polymerswherein the one or more monomers or polymers amounts in the polymericmaterial or the stent after treatment ranges from 0.001% to 10% byweight, preferably ranges from 0.1% to 5% by weight, more preferablyranges from 0.1% to 3% by weight and wherein the stent at bodytemperature is capable to expand from a crimped configuration to adeployed diameter without fracture and have sufficient strength tosupport a body lumen. In one preferred embodiment, the polymericmaterial is treated wherein the treatment comprises inducing orincorporation of monomers or polymers wherein the one or more monomersor polymers amounts in the polymeric material or the stent aftertreatment ranges from 0.001% to 10% by weight, preferably ranges from0.1% to 5% by weight, more preferably ranges from 0.1% to 3% by weightand wherein the one or more monomers or polymers substantially does notaffect degradation of the stent (preferably does not affect degradationthe stent. In other embodiments, the monomer or polymer acceleratesdegradation of the stent) and wherein the stent at body temperature iscapable to expand from a crimped configuration to a deployed diameterwithout fracture and have sufficient strength to support a body lumen.In one preferred embodiment, the polymeric material is treated whereinthe treatment comprises inducing or incorporation of monomer or polymerwherein the one or more monomer or polymer amounts in the polymericmaterial or the stent after treatment ranges from 0.001% to 10% byweight, preferably ranges from 0.1% to 5% by weight, more preferablyranges from 0.1% to 3% by weight and wherein the one or more monomer orpolymer preferably substantially does not affect the stent degradation(preferably accelerates the stent degradation) and wherein the one ormore monomer or polymer substantially remains in the stent in the rangesdescribed above before deployment of the stent) wherein the stent atbody temperature is capable to expand from a crimped configuration to adeployed diameter without fracture and have sufficient strength tosupport a body lumen. In other embodiments, the one or more monomer orpolymer amounts in the polymeric material or the stent after treatmentranges from 0.1% to 10% by weight, preferably ranges from 1% to 5% byweight, more preferably ranges from 2% to 5%. Examples of monomers orpolymers include lactides, glycolides, caprolactones, lactides andglycolides, lactides and caprolactones to name a few. Incorporation ofmonomers can take place, for example by spraying as described herein, orinducing by radiation. Preferred Tg ranges from 20° C. to 50° C., morepreferred from greater than 37° C. to less than 50° C. Preferredcrystallinity ranges from 1% to 60%, preferably from 1% to 55%, morepreferably from 1% to 45%, most preferably from 1% to 35%. The polymericmaterial preferably has an initial diameter, preferably 1-1.5 times thedeployment diameter of the stent. In a preferred embodiment, the stentis capable of being crimped from an expanded diameter to a crimpeddiameter, and at body temperature is capable to expand from a crimpedconfiguration to a deployed diameter without fracture and havesufficient strength to support a body lumen. Examples of polymericmaterial are materials comprising lactide, lactide and glycolide, orlactides and caprolactones, or a combination thereof.

Further embodiments of the disclosure relate to a method of making abiodegradable endoprosthesis, comprising providing a polymeric article(e.g., a tubular body, such as a polymeric tube) comprising at leastpartially a substantially amorphous or semi-crystalline, biodegradablepolymeric material, wherein crystallinity (e.g., degree ofcrystallinity) of the polymeric material increases after the polymericarticle undergoes a modification (or treatment), and wherein theendoprosthesis is formed from the polymeric article. The polymericmaterial is substantially amorphous or semi crystalline prior to themodification, and may or may not be substantially amorphous after themodification. Further embodiments of the disclosure relate to a methodof making a biodegradable endoprosthesis, comprising providing apolymeric article (e.g., a tubular body, such as a polymeric tube)comprising at least partially of a substantially amorphous orsemi-crystalline biodegradable polymeric material, wherein crystallinity(e.g., degree of crystallinity) of the polymeric material decreasesafter the polymeric material undergoes a treatment, and wherein theendoprosthesis is formed substantially from the polymeric material. Inone embodiment, the polymeric material is substantially amorphous orsemi crystalline prior to the modification, and substantially amorphousafter the modification. In certain embodiments, the modificationcomprises heating, cooling, quenching, pressurizing, vacuuming,crosslinking, addition of an additive, or exposure to radiation orcarbon dioxide, or a combination thereof. The polymeric article can haveany shape, form and dimensions suitable for making the endoprosthesis(e.g., a patterned polymeric tube stent).

In an embodiment, treatment comprises a heat treatment preferably atabout initial diameter to a temperature above its glass transitiontemperature of the polymeric material and below its melting point for aperiod ranging from a fraction of a second to 7 days. The polymericmaterial or the tubular body in one embodiment may be cooled afterheating to a temperature ranging from below ambient temperature toambient temperature over a period ranging from a fraction of a second to7 days. In a preferred embodiment, the polymeric material or the tubularbody initial diameter is approximately 1-1.5 times the stent deploymentdiameter. In one embodiment, the polymeric material or the tubular bodyis treated at diameter between initial diameter and crimped diameter. Ina further embodiment, the treatment comprises heating the tubular bodyto a temperature about or below Tg for a period ranging from a fractionof a second to 7 days. In another embodiment, the heat treatment at thebelow initial diameter comprises heat treatment about or above Tg andbelow Tm for a period ranging from a fraction of a second to 5 hours, orpreferably less than 2 hour, or most preferably less than 60 minutes. Inanother embodiment, the polymeric material or the tubular body afterforming is treated comprising heat at temperature about or less than Tg.In another embodiment, the tubular body after forming and excludingpatterning is treated comprising heat at temperature about or less thanTg. In some cases, the treatment is about Tm or higher. Examples ofmethods of forming the stent polymeric material are by injection moldingor 3D printing. Durations are similar to above ranges. Other suitabletemperatures and times are described herein.

In some embodiments, the diameter of the tubular body or the polymericmaterial or the stent may, at the time of treatment (e.g., treatmentdiameter), be optionally smaller or optionally greater than thedeployment diameter, where the deployment diameter may include, forexample, the diameter of the tubular body or the stent within a lumen.In some embodiments, the treatment diameter may be 1-2 times thedeployment diameter, or 1-1.9 times the deployment diameter, or 1-1.8times the deployment diameter, or 1-1.7 times the deployment diameter,or 1-1.6 times the deployment diameter, or 1-1.5 times the deploymentdiameter, or 1-1.4 times the deployment diameter, or 1-1.3 times thedeployment diameter, or 1-1.2 times the deployment diameter, or 1-1.05times the deployment diameter. In other embodiments, the treatmentdiameter may be 0.95-1 times the deployment diameter. In otherembodiments, the treatment diameter may be 0.9-1 times the deploymentdiameter, or 0.8-1 times the deployment diameter, or 0.7-1 times thedeployment diameter, or 0.6-1 times the deployment diameter, or 0.5-1times the deployment diameter, or 0.4-1 times the deployment diameter,or 0.3-1 times the deployment diameter, or 0.2-1 times the deploymentdiameter. The stent expanded/deployed diameter typically is 2 mm andhigher, 2.5 mm and higher, 3 mm and higher, 3.5 mm and higher, 4 mm andhigher, 4.5 mm and higher, 5 mm and higher, 5.5 mm and higher. In otherembodiments, the stent deployed diameter ranges from 2 mm-25 mm,preferably ranges from 2.5 mm to 15 mm, more preferably from 3 mm to 10mm. The stent length ranges from 1 mm to 200 cm, preferably from 5 mm to60 cm, more preferably from 5 mm to 6 cm.

Another aspect of the invention provides biodegradable implantabledevices (e.g., stents) comprising a polymeric material, or a body (e.g.,a tubular body) that comprises one or more biodegradable polymericmaterials to achieve a desired Tg. In another aspect of the inventionthe treated polymeric material or the tubular body has a desired Tg. Inanother aspect of the invention the tubular body or polymeric materialis treated to control Tg. In another aspect of the invention the tubularbody is treated to control Tg and crystallinity. In another aspect ofthe invention the tubular body is treated to control Tg, crystallinity,and molecular weight. In some embodiments, the one or more materialscomprising the body, or the stent, or the stent material, or the tubularbody or the polymeric material may have a wet or dry glass transitiontemperature (T_(g)) greater than 20° C., or greater than 30° C., orgreater than 31° C., or greater than 32° C., or greater than 33° C., orgreater than about 34° C., or greater than 35° C., or greater than 36°C., or greater than 37° C. In some embodiments, the one or morematerials comprising the body, or the stent, or the tubular body have aT_(g) less than 45° C., or less than 44° C., or less than 43° C., orless than 42° C., or less than 41° C., or less than 40° C., or less than39° C., or less than 38° C., or less than 37° C., or less than 36° C. Insome embodiments, the one or more materials comprising the body, or thestent, or the tubular body have a T_(g) of about 20° C. to about 55° C.,or about 20° C. to about 50° C., or about 31° C. to about 45° C., orabout 32° C. to about 45° C., or about 33° C. to about 45° C., or about34° C. to about 45° C., or about 35° C. to about 45° C., or about 36° C.to about 45° C., or about 37° C. to about 45° C., or about 38° C. toabout 45° C., or about 39° C. to about 45° C., or about 40° C. to about45° C. In some embodiments, the one or more materials comprising thebody, or the stent, or the tubular body have a T_(g) of about 20° C. toabout 45° C., or about 30° C. to about 44° C., or about 30° C. to about43° C., or about 30° C. to about 42° C., or about 30° C. to about 41°C., or about 30° C. to about 40° C., or about 30° C. to about 39° C., orabout 30° C. to about 38° C., or about 30° C. to about 37° C. In someembodiments, the one or more materials comprising the body, or thestent, or the tubular body has a T_(g) greater than 37° C. and less than45° C., or greater than 37° C. and less than 40° C., or greater than 37°C. to less than 50° C., or greater than 37° C. to less than 55° C., orgreater than 38° C. to less than 50° C., or greater than 40° C. and lessthan 50° C., or greater than 45° C. and less than 50° C.

In some embodiments, the one or more materials comprising the body, orthe polymeric material, or the stent, or the stent material, or thetubular body has a T_(g) greater than 35° C. and less than 45° C., orgreater than 36° C. and less than 45° C., or greater than 37° C. andless than 45° C., or greater than 37° C. and less than 40° C. or greaterthan 20° C. and less than 45° C., or greater than 35° C. and less thanor equal to 45° C.

In some embodiments, the one or more biodegradable polymeric materialsor the tubular body or the stent material has elastic modulus at bodytemperature (in aqueous or water or dry) of 0.2 GPa to 20 GPa, or of 0.3GPa to 5 Pa, or greater than 0.35 GPa and less than 3 GPa, or of 0.4 GPato 2.5 GPa, or of about 0.5 Pa to about 1 GPa, or of about 0.35 GPa toabout 0.85 GPa, or of about 0.40 GPa to about 0.75 GPa, or of about 0.45Pa to about 0.70 Pa, or of about 0.50 GPa to about 0.65 GPa, or at least0.2 GPa, or at least 0.3 GPa, or at least 0.4 GPa, or at least 0.5 GPa.In some embodiments, the one or more biodegradable polymeric materials,or the tubular body or the stent may have a percent elongation at breakat body temperature (in aqueous or water or dry) of 20% to 800%, or ofabout 20% to about 300%, or of about 20% to about 200%, or of about 20%to about 100%, or of about 20% to about 50%, or of about 10% to about600%, or of about 10% to about 300%, or of about 5% to about 600%, or ofabout 5% to about 300%, or of about 1% to about 600%, or of about 1% toabout 300%, or of about 1% to about 200%, or of about 1% to about 150%;

In yet further embodiments, the polymeric material comprising the bodyof the device or the biodegradable polymer, or copolymer or polymerblend, or the tubular body comprising the biodegradable polymericmaterial or the stent material; has a tensile yield strength of at least1500 psi, or at least 2000 psi, or at least 2500 psi, or at least 3000psi, or at least 4000 psi, or at least 5000 psi. In yet furtherembodiments, the polymeric stent material has a tensile yield strengthranging from 1500 psi to 6000 psi, or between 200 psi and 5000 psi. Inanother embodiment, the biodegradable polymeric material or the tubularbody or the stent material; has stiffness of at least 1000 MPa, or atleast 1500 MPa, or at least 2000 MPa, or at least 2500 MPa, or at least3000 MPa, or at most 5000 MPa, or at most 4000 MPa; when measured atbody temperature (in aqueous or water or dry). In yet furtherembodiments, the biodegradable polymeric material or the tubular body orthe stent material; has elastic modulus of at least 250 MPa, or at least350 MPa, or at least 400 MPa, or at least 450 MPa, or at least 500 MPa;when measured at body temperature (in aqueous or water or dry). In yetanother embodiment, the material comprising the body or thebiodegradable polymer or copolymer or polymer blend, or the tubular bodycomprising the biodegradable polymer, or the stent; has a percentelongation at break when measure at body temperature (wet or dry) ofabout 20% to about 800%, or of about 20% to about 300%, or of about 20%to about 200%, or of about 20% to about 100%, or of about 20% to about50%, or of about 10% to about 600%, or of about 10% to about 300%, or ofabout 5% to about 600%, or of about 5% to about 300%, or of about 1% toabout 600%, or of about 1% to about 300%, or of about 1% to about 200%,or of about 1% to about 150%. In other embodiments, the biodegradablepolymer, copolymer or polymer blend or tubular body comprising thebiodegradable polymer material or stent prosthesis material hasstiffness at body temperature (in aqueous or water or dry) of about0.4N/mm2 to about 2N/mm2, or of about 0.5N/mm2 to about 1.5N/mm2, or ofabout 0.7N/mm2 to about 1.4N/mm2, or of about 0.8N/mm2 to about 1.3N/mm2In other embodiments, the biodegradable polymer or copolymer or polymerblend or tubular body comprising the biodegradable polymer material orprosthesis; has elastic modulus at body temperature, of about 0.2 GPa toabout 20 GPa, or of about 0.3 GPa to about 5 GPa, or of about 0.4 GPa toabout 2.5 GPa, or of about 0.5 GPa to about 1 GPa, or at least 0.2 GPa,or at least 0.3 GPa, or at least 0.4 GPa, or at least 0.5 GPa. In otherembodiments, the biodegradable polymer or copolymer or polymer blend ortubular body comprising the biodegradable polymer material or prosthesismaterial; has yield strain at body temperature of at most 20%, or atmost 15%, preferably at most 10%, more preferably at most 5%, at bodytemperature (in aqueous or water or dry). In yet another embodiment, theprosthesis has radial strength sufficient to support a body lumen. Inyet another embodiment, the biodegradable polymer or copolymer ortubular body or stent prosthesis; has a radial strength in an aqueousenvironment at about 37° C. (e.g., body temperature) of about 2 psi toabout 25 psi, or of about 5 psi to about 22 psi, or of about 7 psi toabout 20 psi, or of about 9 psi to about 18 psi. In yet anotherembodiment, the biodegradable polymer or copolymer or tubular body orstent prosthesis; has a radial strength at body temperature (in aqueousor water or dry) of greater than 2 psi, or greater than 8 psi, orgreater than 10 psi, or greater than 15 psi. Radial strength can bemeasured in a variety of methods known in the art. For example the flatplate method or iris method or other known methods. Radial force can bemeasured with several methods known in the art. For example when thestent radial strength is not sufficient to support a body lumen, or theexpanded diameter is reduced by a substantial amount, or reduced by atleast 15%, or reduced by at least 20%, or reduced by at least 25%, orreduced by at least 50%. In other embodiments, the biodegradablecopolymer, or polymer blend, or polymer, or tubular body comprising thebiodegradable polymer, or prosthesis has a % recoil in an aqueousenvironment at 37° C. of about −20% to about 20%, or of about −15% toabout 15%, or of about −10% to about 10%, or of about −10% to about 0%,or of about 0% to about 10%, or of about 3% to about 10%, or of about 4%to about 9%, or less than 25%, or less than 20%, or less than 15%, orless than 10%, or less than 5%; after expansion from a crimped state. %recoil is measured in a variety of ways in-vitro or in-vivo with methodsknown in the art. For example in-vitro % recoil can be measured byexpanding the stent in an aqueous environment at about 37° C. inside atube or unconstrained and measuring % recoil after expansion using lasermicrometer. For an example for in-vivo % recoil measurement using QCAsee, e.g., Catheterization and Cardiovascular Interventions, 70:515-523(2007). In yet another embodiment, the biodegradable polymer orcopolymer or tubular body or prosthesis, has a radial strength (in anaqueous environment or dry at 37° C. from about 1 minute to about 1 dayafter expansion) of about 2 psi to about 25 psi; wherein the radialstrength increases by about 1 psi to about 20 psi, or by about 2 psi toabout 15 psi, or by about 3 psi to about 10 psi, or by about 4 psi toabout 8 psi, after being in such an aqueous or dry environment for about1 day to about 60 days. In other embodiments, the biodegradable,polymer, or copolymer, or polymer blend, or tubular body, or stentmaterial; is substantially amorphous, or substantially semi crystalline,or substantially crystalline; after modification, or beforemodification, or after radiation, or before implantation into amammalian body lumen. In other embodiments, the biodegradable polymer,or copolymer or polymer blend, or tubular body, or stent; issubstantially amorphous before and after modification, or substantiallyamorphous before a modification and substantially semi crystalline aftermodification, or substantially amorphous before a modification andsubstantially crystalline after modification, or substantially semicrystalline before a modification and substantially amorphous aftermodification, or substantially semi crystalline before a modificationand substantially semi crystalline after modification, or substantiallysemi crystalline before a modification and crystalline aftermodification, or substantially crystalline before modification andsubstantially semi crystalline after a modification, or substantiallycrystalline before a modification and substantially amorphous after amodification, or substantially crystalline before a modification andafter modification.

In other embodiments, the biodegradable polymer or copolymer or polymerblend or tubular body or stent has longitudinal shrinkage of about 0% toabout 30%, or of about 5% to about 25%, or of about 7% to about 20%, orof about 10% to about 15%; when heated (e.g. in an oven) at temperaturesranging from about 30° C. to about 150° C. (with or without a mandrelinserted into the copolymer or tubular body or prosthesis for a timeranging from about 30 minutes to about 24 hours); or upon or afterexpansion of the stent from a crimped state to an expanded state at bodytemperature. In yet another embodiment, the longitudinal shrinkage isless than 30%, or less than 25%, or less than 20%, or less than 15%, orless than 10%, of the original length upon or after expansion of thestent from a crimped state to an expanded state at body temperature. Inyet another embodiment, the stent or polymer material or polymer tubehas longitudinal shrinkage of less than about 25% or less, or about 15%or less, or about 10% or less, or about 5% or less, or about 1-25%, orabout 5-15%, after being in aqueous condition at about 37° C. in vitroor in vivo for about 1 minute or less, or about 5 minutes or less, orabout 15 minutes or less, or after expansion from the crimped state atbody temperature. In other embodiments the stent or polymer material orpolymer tube has longitudinal shrinkage of less than about 25% or less,or about 15% or less, or about 10% or less, or about 5% or less, orabout 1-25%, or about 5-15%, after being in aqueous condition at about37° C. in vitro or in vivo for about 1 minute or less, or about 5minutes or less, or about 15 minutes or less, or after expansion fromthe crimped state. In yet another embodiment, the stent or polymericmaterial or tubular body has longitudinal lengthening of less than 25%,or 15% or less, or 10% or less, or 5% or less, or 1-25%, or 5-15%, afterbeing in aqueous condition at about 37° C. in vitro or in vivo for about1 minute or less, or about 5 minutes or less, or about 15 minutes orless, or after expansion from the crimped state at body temperature. Inyet another embodiment, the amorphous, or semicrystalline, orcrystalline polymeric material has internal stresses, or longitudinalshrinkage of no more than 15% from before a modification to aftermodification. In yet another embodiment, the polymer comprises apolymer, or a co-polymer, or a blend of polymers, or a mixture ofpolymers, or a blend of polymer and at least one monomer, or a blend ofco-polymer and at least one monomer, or a combination thereof. In yetanother embodiment, the polymer blend, copolymer, or mixture ofpolymers, substantially does not exhibit phase separation. In yetanother embodiment, the polymer or tubular body or prosthesis, isporous; such that it will grow in the radial direction by about 0.025 mmto about 1 mm when soaked in an aqueous or dry environment at about 37°C. from about 1 minute to about 15 minutes. In another embodiment, thecopolymer material, or tubular body, or prosthesis, has a texturedsurface, or non uniform surface, or surface with ridges, or bumpysurface, or surface with grooves, or wavy surface. The distance betweenthe peak and trough of the surface texture range from about 0.01 micronto about 30 micron, or from about 0.1 micron to about 20 micron, or fromabout 1 micron to about 15 micron.

In some embodiments, the one or more biodegradable polymeric materials,or the tubular body or the stent may have a radial strength in anaqueous environment at about 37° C. of about 2 psi to about 25 psi, orof about 5 psi to about 22 psi, or of about 7 psi to about 20 psi, or ofabout 9 psi to about 18 psi. In yet another embodiment, thebiodegradable polymer or copolymer or tubular body or prosthesis; has aradial strength in an aqueous or dry environment at body temperature of,greater than 3 psi, or greater than 5 psi, or greater than 8 psi, orgreater than 10 psi, or greater than 15 psi.

In some embodiments, the biodegradable copolymer, or polymer blend, orpolymer, or tubular body comprising the biodegradable polymer, orprosthesis has a % recoil in an aqueous or dry environment at 37° C. ofabout −20% to about 20%, or of about −15% to about 15%, or of about −10%to about 10%, or of about −10% to about 0%, or of about 0% to about 10%,or of about 3% to about 10%, or of about 4% to about 9%, or about 10% toabout 20%, or about 15% to about 20%, or about 10% to about 15% or lessthan 25%, or less than 20%, or less than 15%, or less than 10%, or lessthan 5% after expansion to a deployed configuration from a crimpedstate.

The one or more biodegradable polymeric materials, or the tubular body,or the stent may optionally undergo treatment such as heating. In someembodiments, the one or more biodegradable polymeric materials, or thetubular body, or the stent may undergo longitudinal shrinkage of about0% to about 30%, or of about 5% to about 25%, or of about 7% to about20%, or of about 10% to about 15%. In other embodiments, thelongitudinal (e.g., scaffold) shrinkage is less than 30%, or less than25%, or less than 20%, or less than 15%, or less than 10%, of theoriginal length. In other embodiments, the stent or polymer material orpolymer tube has longitudinal shrinkage of about 25% or less, or about15% or less, or about 10% or less, or about 5% or less, or about 0-30%,or about 1-25%, or about 5-15%. In some embodiments, treatment mayinclude heating (e.g. in an oven) at temperatures ranging from about 30°C. to about 150° C. (with or without a mandrel inserted into the polymeror copolymer or tubular body or stent for a time ranging from about 30minutes to about 24 hours); or expansion of the one or morebiodegradable polymeric materials, or the tubular body, or the stentfrom a crimped state to an expanded state in an aqueous or dryenvironment at about 37° C. in vitro or in vivo for about 1 minute orless, or about 5 minutes or less, or about 15 minutes or less.

In further embodiments, the material comprising the body of the deviceor the biodegradable polymer, copolymer or polymer blend, or the tubularbody comprising the biodegradable polymer, or the stent; is, or hascrystals, crystalline regions, or polymer chains that are: substantiallynot uniaxially oriented, or not circumferentially oriented, or notlongitudinally oriented, or not biaxially oriented. In otherembodiments, the biodegradable copolymer has crystals, crystallineregions, molecular architecture, structural order, orientation, orpolymer chains that are: substantially not uniform, or has low degree oforder, or has varying degree of order, or is not substantially orientedas a result of not performing at least one of pressurizing andstretching of the tubular body, or is at least partially oriented as aresult of spraying or dipping or crystallization or recrystallization,or radiation, or is at least partially oriented as a result of solventevaporation or annealing or radiation, or is substantially not oriented,or not uniformly oriented, or low order oriented, or varying degreeoriented, or randomly oriented, as a result of spraying or dipping, orsolvent evaporation, or annealing, or radiation, or crystallization orrecrystallization. In yet another embodiment, the biodegradablecopolymer has crystals, crystalline regions, molecular architecture,structural order, orientation, or polymer chains that are: substantiallyoriented, or oriented, or biaxially oriented, or uniaxially oriented, ororiented in a direction that is longitudinal, or oriented in a directionthat is circumferential, or oriented in a direction that is notlongitudinal or circumferential, or oriented as a result of at least oneof pressurizing the tube or stretching or drawing the tube, or orientedas a result of modification or treatment.

In further embodiments, the material comprising the body of the deviceor the biodegradable polymer, copolymer or polymer blend, or the tubularbody comprising the biodegradable polymer, or the stent; is, or hascrystals, crystalline regions, or polymer chains that are: substantiallynot uniaxially oriented, or circumferentially oriented, orlongitudinally oriented, or biaxially oriented. In other embodiments,the biodegradable copolymer has crystals, crystalline regions, moleculararchitecture, structural order, orientation, or polymer chains that are:substantially not uniform, or has low degree of order, or has varyingdegree of order, or is not substantially oriented as a result of notperforming at least one of pressurizing and stretching of the tubularbody, or is at least partially oriented as a result of spraying ordipping or crystallization or recrystallization, or radiation, or is atleast partially oriented as a result of solvent evaporation or annealingor radiation, or is substantially not oriented, or not uniformlyoriented, or low order oriented, or varying degree oriented, or randomlyoriented, as a result of spraying or dipping, or solvent evaporation, orannealing, or radiation, or crystallization or recrystallization. In yetanother embodiment, the biodegradable copolymer has crystals,crystalline regions, molecular architecture, structural order,orientation, or polymer chains that are: substantially oriented, ororiented, or biaxially oriented, or uniaxially oriented, or oriented ina direction that is longitudinal, or oriented in a direction that iscircumferential, or oriented in a direction that is not longitudinal orcircumferential, or oriented as a result of at least one of pressurizingthe copolymer tube or stretching or drawing the tube, or oriented as aresult of modification or treatment.

In one embodiment, controlling the orientation of the polymeric materialachieves the desired crystallinity, or Tg. In another embodiment, thepolymeric material orientation is controlled such that the stent iscapable to be crimped from an expanded condition to a crimped condition.In another embodiment, the polymeric material orientation is controlledsuch that the stent is capable to be expanded to a deployed diameterfrom a crimped configuration. In another embodiment, the polymericmaterial orientation is controlled such that the stent is capable to beexpanded from a crimped configuration to a deployed configurationwithout fracture. In another embodiment, the polymeric materialorientation is controlled such that the material has sufficient strengthto support a body lumen. In a preferred embodiment, the polymericmaterial orientation is controlled by pressurizing the polymericmaterial with a medium such as gas such as CO₂ wherein the orientationcontrol affects crystallinity to a range from 1% to 35%, or 1% to 45%,or 1% to 55%.

In some embodiments, the material (e.g., polymeric material) comprisingthe body of the device or the biodegradable copolymer or polymer has aweight-average molecular weight (M_(W)) of at least about 30,000 daltons(30 kDa), 60,000 daltons, 90 kDa, 120 kDa, 150 kDa, 180 kDa, 210 kDa, or240 kDa, or 500 kDa, or 750 kDa, or 1000 kDa. In an embodiment, thematerial (e.g., polymeric material) comprising the body of the device orthe biodegradable copolymer or polymer has an M_(W) of at least about120 kDa. In further embodiments, the material (e.g., polymeric material)comprising the body of the device or the biodegradable copolymer orpolymer has an M_(W) of about 30 kDa to about 800 kDa, or about 30 kDato about 700 kDa, or about 30 kDa to about 600 kDa, or about 30 kDa toabout 500 kDa, or about 30 kDa to about 400 kDa, or about 30 kDa toabout 300 kDa, or about 60 kDa to about 900 kDa, or about 90 kDa toabout 600 kDa, or about 120 kDa to about 400 kDa, or about 150 kDa toabout 250 kDa, or about 80 kDa to about 250 kDa; before treatment, orafter treatment, of the stent prosthesis or the polymeric material. Inan embodiment, the material (e.g., polymeric material) comprising thebody of the device or the biodegradable copolymer or polymer has a M_(W)of about 120 kDa to about 250 kDa; before treatment, or after treatment,of the stent prosthesis.

In some embodiments, biodegradable polymeric materials may becopolymers, such as block copolymers or random copolymers. In someembodiments, two or more biodegradable polymeric materials may be usedas part of a tubular body or prosthesis or stent (e.g., as a polymerblend). In some cases, co-polymeric and homopolymeric materials may beblended. Biodegradable polymeric materials may include poly-DL-lactide,polylactide-co-glycolactide, or other polymers as described herein. Insome embodiments, the tubular body or prosthesis or stent may alsoinclude one or more monomers of the polymers that comprise the stent, orof other polymers. In some cases, the one or more monomers may becovalently bonded to the one or more polymers. In some embodiments, thetwo or more biodegradable polymeric materials may remain insubstantially the same phase after about 1 second, or 10 seconds, or 1minute, or 10 minutes, or 1 hour, or 10 hours, or 1 day, or 10 days, or1 month, or 6 months, or 1 year, or 2 years, or 5 years of deploymentand/or treatment. In some embodiments, the two or more biodegradablepolymeric materials may have a T_(g) within 2° C., or within 4° C., orwithin 6° C., or within 8° C., or within 10° C., or within 12° C., orwithin 14° C., or within 16° C., or within 18° C., or within 20° C. ofeach other.

In some embodiments, the polymeric material comprises monomer. Infurther embodiments, the polymeric material comprises less than 10% (byweight), or less than 5% (by weight), or less than 1% (by weight), orless than 0.5% (by weight), or less than 0.25% (by weight) monomer. Inother embodiments, the polymeric material comprises 0-10% (by weight) ofmonomer.

In a preferred embodiment, the polymeric material comprises one or moreco-polymers, and to this polymeric material is added about 0.1% or less,or about 0.5% or less, or about 1% or less, or about 2% or less, orabout 3% or less, or about 4% or less, or about 5% or less, or about 6%or less, or about 7% or less, or about 8% or less, or about 9% or less,or about 10% or less monomer. In another embodiment, the polymericmaterial further comprising one or more of the co-polymers, or anothermonomer, or another polymer, or another co-polymer. In further preferredembodiments, the addition of monomer, polymer or copolymer does notchange the Tg of the polymeric material substantially. In otherpreferred embodiments, the addition of monomer, polymer, or copolymerdoes not change the Tg of the polymeric material by more than 10° C., orby more than 5° C., or by more than 3° C. than the polymeric materialwithout added monomer, polymer, or copolymer. In other preferredembodiments, the addition of monomer, polymer, or copolymer does notexhibit phase separation from the polymeric material after treatmentand/or before deployment. In other preferred embodiments, the polymericmaterial comprises less than about 100 micrograms, or less than about 50micrograms, or less than about 25 micrograms or monomer (such asunreacted monomer), polymer, or copolymer per milligram of stent. Inother preferred embodiments, the addition of monomer, polymer orcopolymer does not interfere with the expansion of stent from crimpedstate to expanded state, and the expansion can occur without fracture.In other preferred embodiments, the addition of monomer, polymer, orcopolymer does not change crystallinity of the polymeric material, whichmay be more than about 1% and less than about 30%, or more than about 0%and less than about 35%, or less than 35%, or less than 30%, or lessthan 25%, or less than 20%, or less than 15%, or less than 10%, or lessthan 5%, or greater than 0%, or greater than 5%, or greater than 10%, orgreater than about 15%, or greater than about 20%, or greater than about25%, or greater than about 30%, or greater than about 35%. In otherpreferred embodiments, combination of polymeric material and monomer,polymer, or copolymer comprising the body, or the stent, or the tubularbody may have a crystallinity of about 0% to less than 35%, or about 0%to less than 30%, or about 0% to less than 25%, or about 0% to less than20%, or about 0% to less than 15%, or about 0% to less than 10%, orabout 0% to less than 5%. In other preferred embodiments, addition ofmonomer, polymer or copolymer does not change the molecular weight ofthe polymeric material, which can be in the range from about 30 kDa toabout 700 kDa. In further preferred embodiments, the unreacted monomer,polymer or copolymer comprises glycolic acid, lactide, polyglycolicacid, lactide-co-glycolide, caprolactone, polycaprolactone,lactide-co-caprolactone, and combinations thereof.

In some embodiments, the biodegradable stent or tube comprises a bodywhich comprises a biodegradable polymer, or copolymer, polymer blends,copolymers, and/or polymer/monomer mixtures wherein the polymer materialis configured to be capable of being balloon expandable andself-expanding at body temperature of about 37° C. In one embodiment,prior to being balloon-expanded, the stent may self-expand by about0.001-0.025 inches, or about 0.003-0.015 inches, or about 0.005-0.10inches, or about 0.001 inches or more, or 0.003 inches or more, or 0.005inches or more, or 0.010 inches or more, or 0.025 inch or more, or byabout 0.05%, or about 0.1%, or about 0.25%, or about 0.5%, or about 1%,or more than an initial crimped diameter of the stent, after being inaqueous condition at about 37° C. in vitro or in vivo for about 1 minuteor less, or about 5 minutes or less, or about 15 minutes or less, orabout 30 minutes or less, or about 1 hour or less, or about 2 hours orless, or about 3 hours or less, or about 4 hours or less, or about 6hours or less, or about 12 hours or less, or about one day or less.Optionally, the stent is constrained from self-expanding using a sheathor other means and then such constraining means is removed, disengaged,or withdrawn, or released after the stent is positioned for deployment,allowing the stent to self-deploy. The stent in a preferred embodimentfurther self expands after balloon deployment by about 0.01 mm to about0.5 mm, or about 0.05 mm to about 0.3 mm, within about 30 seconds ormore, or about 1 minute or more, or about 10 minutes or more, or about 1hour or more, or about 12 hours or more, or about 24 hours or more.

In some embodiments, the one or more biodegradable polymeric materials,or the tubular body, or the stent degrade over time. Degradation mayoccur in vitro or in vivo. Degradation may occur after about 1 day, orabout 5 days, or about 10 days, or about 1 month, or about 2 months, orabout 6 months, or about 1 year in aqueous condition (e.g., in aqueoussolution, water, saline solution or physiological conditions) at about37° C. in vitro or in vivo. The one or more biodegradable polymericmaterials or the tubular body may substantially degrade within 2 years,or 1.5 years, or 1 years, or 9 months, or 6 months.

In some embodiments, the body of the device, or the stent, or thematerial comprising the body of the device, or the material comprisingone or more layers of the body of the device, comprises one or morebiologically active agents. In some embodiments, the biologically activeagent(s) are selected from the group consisting of anti-proliferativeagents, anti-mitotic agents, cytostatic agents, anti-migratory agents,immunomodulators, immunosuppressants, anti-inflammatory agents,anticoagulants, anti-thrombotic agents, thrombolytic agents,anti-thrombin agents, anti-fibrin agents, anti-platelet agents,anti-ischemia agents, anti-hypertensive agents, anti-hyperlipidemiaagents, anti-diabetic agents, anti-cancer agents, anti-tumor agents,anti-angiogenic agents, angiogenic agents, anti-bacterial agents,anti-fungal agents, anti-chemokine agents, and healing-promoting agents.In certain embodiments, the body of the device comprises ananti-proliferative agent, anti-mitotic agent, cytostatic agent oranti-migratory agent. In further embodiments, the body of the devicecomprises an anticoagulant, anti-thrombotic agent, thrombolytic agent,anti-thrombin agent, anti-fibrin agent or anti-platelet agent inaddition to an anti-proliferative agent, anti-mitotic agent, cytostaticagent or anti-migratory agent. It is appreciated that specific examplesof biologically active agents disclosed herein may exert more than onebiological effect. Examples of anti-proliferative agents, anti-mitoticagents, cytostatic agents and anti-migratory agents include withoutlimitation rapamycin and its derivatives and metabolites.

In some embodiments, the stent or body of the device can comprise one ormore biologically active agents, and/or one or more additives such ascarbon nano fibers or tubes. The additives can serve any of a variety offunctions, including controlling degradation, increasing the strength,increasing elongation, controlling Tg, or/and increasing toughness ofthe material (e.g., polymeric material) comprising the body of thedevice (or the material comprising a coating on the body), and/orincreasing crystallinity.

In another embodiment, the stent or tubular body comprises radiopaquemarkers. Radiopaque markers can be metallic such as gold, platinum,iridium, bismuth, or combination thereof, or alloys thereof. Radiopaquemarkers can also be polymeric material. Radiopaque markers can beincorporated in the stent or tubular body when it is being formed orincorporated into the stent or the tubular body after forming.

In some embodiments, one or more coatings can be applied onto the bodyof the device. Each of the coatings can contain one or morebiodegradable polymers, one or more non-degradable polymers, one or moremetals or metal alloys, one or more biologically active agents, or oneor more additives, or a combination thereof. The coating(s) can serveany of a variety of functions, including controlling degradation of thebody of the device, improving or controlling physical characteristics(e.g., strength, recoil, toughness) of the device, and delivering one ormore biologically active agents to a site of treatment.

In some embodiments, depending in part on the type of device it is, thebiodegradable implantable device described herein can be used to treator prevent a wide variety of diseases, disorders and conditions, orpromote a wide variety of therapeutic effects. In some embodiments, thebiodegradable device is implanted in a subject for treatment orprevention of a disorder or condition, or delivery or a drug, orpromotion of a therapeutic effect, selected from the group consisting ofwound healing, hyper-proliferative disease, cancer, tumor, vasculardisease, cardiovascular disease, coronary artery disease, peripheralarterial disease, ENT or nose disorder, atherosclerosis, thrombosis,vulnerable plaque, stenosis, restenosis, ischemia, myocardial ischemia,peripheral ischemia, limb ischemia, hyper-calcemia, vascularobstruction, vascular dissection, vascular perforation, aneurysm,vascular aneurysm, aortic aneurysm, abdominal aortic aneurysm, cerebralaneurysm, chronic total occlusion, patent foramen ovale, hemorrhage,claudication, diabetic disease, pancreas obstruction, kidneyobstruction, bile duct obstruction, intestine obstruction, duodenumobstruction, colon obstruction, ureter obstruction, urethra obstruction,sphincter obstruction, airway obstruction, anastomosis, anastomoticproliferation of artery, vein or artificial graft, bone injury, bonecrack, bone fracture, osteoporosis, skeletal defect, bone defect, weakbone, bone thinning, improper bone union or healing, fusing bone, fusionof adjacent vertebrae, osteochondral defect, chondral defect, cranialdefect, scalp defect, calvarial defect, craniofacial defect,craniomaxillofacial defect, segmental bone loss, thoracic cage defect,cartilage defect, cartilage repair, cartilage regeneration,bone-cartilage bridging, bone-tendon bridging, spinal disorder,scoliosis, nerve damage, nerve injury, nerve defect, nerve repair, nervereconstruction, nerve regeneration, herniation, abdominal herniation,disc herniation, acute or chronic low back pain, discogenic pain,trauma, abdominal wall defect, septal repair, burn injury, facialreconstruction, facial regeneration, aging, and contraception. Thebiodegradable device can also be used outside the body, e.g., in tissueengineering to generate tissue.

When the biodegradable device is a stent, the stent can also be used totreat or prevent a wide variety of diseases, disorders and conditions.In some embodiments, the biodegradable stent is implanted in a subjectfor treatment or prevention of obstruction, occlusion, constriction,stricture, narrowing, stenosis, restenosis, intimal hyperplasia,collapse, dissection, thinning, perforation, kinking, aneurysm, failedaccess graft, cancer or tumor of a vessel, passage, conduit, tubulartissue or tubular organ, such as an artery, vein, peripheral artery,peripheral vein, subclavian artery, superior caval vein, inferior cavalvein, popliteal artery, popliteal vein, arterial duct, coronary artery,carotid artery, brain artery, aorta, ductus arteriosus, rightventricular outflow tract conduit, transitional atrioventricular canal,interatrial septum, iliac artery, common iliac artery, external iliacartery, internal iliac artery, iliac vein, internal pudendal artery,mammary artery, femoral artery, superficial femoral artery, femoralvein, pancreatic artery, pancreatic duct, renal artery, hepatic artery,splenic artery, biliary artery, bile duct, stomach, small intestine,duodenum, jejunum, ileum, large intestine, cecum, colon, rectosigmoidcolon, sphincter, rectum, colorectum, ureter, urethra, prostatic duct,pulmonary artery, aortopulmonary collateral artery, aortopulmonarycollateral vessel, airway, nasal passage, nostril, throat, pharynx,larynx, esophagus, epiglottis, glottis, trachea, carina, bronchus,bilateral main bronchus, intermediate branch bronchus, transbronchialpassage, or tracheobronchus.

In certain embodiments, the biodegradable device is an endoprosthesis orstent. Non-limiting examples of stents include vascular stents, coronarystents, coronary heart disease (CHD) stents, carotid stents, brainaneurysm stents, peripheral stents, peripheral vascular stents, venousstents, femoral stents, superficial femoral artery (SFA) stents,pancreatic stents, renal stents, biliary stents, intestinal stents,duodenal stents, colonic stents, ureteral stents, urethral stents,prostatic stents, sphincter stents, airway stents, tracheobronchialstents, tracheal stents, laryngeal stents, esophageal stents, singlestents, segmented stents, joined stents, overlap stents, tapered stents,and bifurcated stents. In certain embodiments, the biodegradable deviceis a vascular or coronary stent.

In some embodiments, the endoprosthesis design and pattern can be anysuitable pattern of the type employed in conventional endoprostheses toserve the intended purpose of the device. A variety of exemplarypatterns are set forth in (but not limited to) U.S. patent applicationSer. No. 12/016,077, which is incorporated herein by reference in itsentirety.

In certain embodiments, the material (e.g., polymeric material)comprising or comprising the body of the biodegradable implantabledevice or the biodegradable copolymer or polymer:

has a degree of crystallinity, or % crystallinity by XRD or DSC, ofabout 5% to about 30% by weight or volume;

has a T_(g) of greater than 37° C. and less than 50° C.;

has a tensile yield strength of at least about 1500 psi;

Mw of 30 kDa to 600 kDa; and

has a % elongation at break or failure or yield of about 15% to about300%; and radially expandable from crimped configuration to expandedconfiguration without fracture at body temperature.

In certain embodiments, the material (e.g., polymeric material)comprising the body of the biodegradable implantable device or thebiodegradable copolymer or polymer:

has a degree of crystallinity, or % crystallinity by XRD or DSC, ofabout 30%;

has a T_(g) of greater than 37° C. to less than 47° C.;

has a tensile yield strength of at least about 1500 psi; and

has a % elongation at break or failure or yield of about 15% to about300%.

In certain embodiments, the biodegradable devices and the biodegradablepolymers have a rough exterior, or texture as depicted in FIG. 5A forexample. The preferred texture is such that the surface has severalbumps, or/and such bumps are not oriented in an uniform manner. Thistexture can be achieved in a variety of ways including spraying as anexample. Such texture is different from the texture show in FIG. 5B,wherein the texturing has an orientation, in this case the orientationbeing in the horizontal direction. Such horizontally oriented texturingis in some embodiments can be achieved by die extrusion. In certainother embodiments, the biodegradable devices and the biodegradablepolymers have both types of texturing described herein. In a preferredembodiment, orientation of the device may be controlled.

In some embodiments, the stent is deployed in a main vessel across aside branch, and the stent of the invention allows for insertion of aguidewire and/or balloon catheter through openings between stent struts,and enabling inflation through the openings of stent struts to increaseor expand interstrut opening to the branch. The stent allows for aguidewire and/or balloon catheter through the opening to expand at leastone transverse dimension to access and treat the side branch withballoon inflation, or additional stent implantation or drug deliverytreatments. The stent expanded diameter/transverse dimension in oneembodiment is substantially maintained after balloon expansion andremoval of the balloon. In another embodiment, the expandeddiameter/transverse dimension is decreased after balloon expansion andremoval of the balloon. In a preferred embodiment, the decrease is atleast 20% from the expanded transverse dimension. In a preferredembodiment, the decrease is at least 20% from the expanded transversedimension and less than 75%. In a third embodiment, the expandedtransverse dimension becomes larger after balloon expansion and removalof the balloon, preferably larger by at least 1%, or by at least 5%, orby at least 10% from the balloon expanded transverse dimension.Typically, changes in the transverse dimension occur within 24 hours orless, or 12 hours or less, or 9 hours or less, or 6 hours or less, or 3hours or less, or 1 hour or less, or 30 minutes or less.

In one embodiment, the stent struts are capable of expanding along oneor more than one dimension or directional dimension upon ballooninflation through the stent strut openings along the longitudinal,radial, or circumferential dimensions. In a preferred embodiment, thestent struts are capable to expand in one or more transverse dimensionswithout fracture. In a preferred embodiment, the expanded transversedimension of the stent struts remains substantially the same, andwithout fracture. In a preferred embodiment, the expanded transversedimension of the stent struts further expands or increase, and withoutfracture. In a preferred embodiment, the expanded transverse dimensionof the stent struts further contracts or decrease, and without fracture.

In another embodiment, the balloon expands stent struts in at least theradial transverse dimension, further self expands to align with vesselwall, or self expand to oppose the vessel wall, or self expands by atleast 0.01 mm.

The invention provides polymeric materials, including biodegradablestents, and methods of their fabrication. Various aspects of theinvention described herein may be applied to any of the particularapplications set forth below or in any other type of setting. Theinvention may be applied as a standalone system or method, or as part ofan integrated system or method. It shall be understood that differentaspects of the invention can be appreciated individually, collectively,or in combination with each other.

Other goals and advantages of the invention will be further appreciatedand understood when considered in conjunction with the followingdescription and accompanying drawings. While the following descriptionmay contain specific details describing particular embodiments of theinvention, this should not be construed as limitations to the scope ofthe invention but rather as an exemplification of preferableembodiments. For each aspect of the invention, many variations arepossible as suggested herein that are known to those of ordinary skillin the art. A variety of changes and modifications can be made withinthe scope of the invention without departing from the spirit thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts an example of stent pattern having substantially W and/orV-shaped cells;

FIG. 2 illustrates an example of raised portions (poofs) formed on theballoon of a balloon-catheter which hold, cap and/or extend over theproximal and/or distal ends of a stent to retain the stent substantiallyin place on the balloon during delivery;

FIG. 3 depicts an example of stent pattern having lockable elements thatare designed to retain the stent on a balloon-catheter;

FIG. 4 depicts in a crimped state an example of pattern of a stent cutfrom a polymeric tube;

FIGS. 5A and 5B depict examples of the surface features of an embodimentof a device;

FIG. 6 shows a typical series of OCT images following implant of anembodiment of a device in a porcine model;

FIG. 7 shows the stent diameter at various time points following implantof an embodiment of a device in a porcine model;

FIG. 8 depicts an example of a method used to calculate % stenosisfollowing implant of an embodiment of a device in a porcine model;

FIG. 9 shows the observed % stenosis following implant of an embodimentof a device in a porcine model;

FIG. 10 shows an example of vascular response at 180 days followingimplant of an embodiment of a device in a porcine model;

FIG. 11 shows the PK results following implant of an embodiment of adevice in a porcine model;

FIGS. 12A, 12B, and 12C show the degradation of the implant in a porcinemodel of an embodiment.

FIG. 13 shows embodiments of compressive radial stress and recoil ofbioresorbable, drug eluting stent (BDES) versus bare metal stent (BMS);

FIG. 14 shows embodiments of flexibility, and conformability of BDES vs.BMS;

FIG. 15 shows a plot of a stent diameter over time in a water bath at37° C. in one embodiment;

FIG. 16 shows a plot of M_(w) of stents of Design A and Design Bembodiments over time in a water bath at 37° C.;

FIG. 17 shows a plot of strength of stents of Design A and Design Bembodiments over time in a water bath at 37° C.;

FIG. 18 shows a stent balloon expanded to about 3.6 mm outer diameter(OD) wherein the stent further self expands within one hour by at least0.1 mm;

FIGS. 19A and 19B show balloon expanded stents at least maintain thediameter of tubular stents of design A, design B, and design C,embodiments over time (1 month and 6 months, respectively);

FIG. 20 shows changes in the strength of tubular stents of design A,design B, and design C embodiments over time;

FIG. 21 shows the decrease of molecular weight of stent over one to twoyears with radial strength sufficient to support a blood vessel for atleast 2 months;

FIG. 22A illustrates a stent scaffold deployed in a block, with a finaldiameter smaller than block simulating malapposed struts, and FIG. 22Billustrates stent scaffold within 5-10 minutes of soaking in water at 37C, with gaps “resolved”, or apposed to the wall and no malappositionpresent;

FIG. 23A illustrates a stent scaffold expanded in a mock artery with a0.3 mm mandrel on the side, FIG. 23B illustrates a stent scaffold withmandrel removed, confirming that a gap is still present, FIG. 23Cillustrates a stent scaffold shows a stent scaffold after 10 minutes ofsoaking in water at 37° C., and FIG. 23D illustrates a stent scaffoldafter 20 minutes of soaking in water where in the stent is apposedagainst the vessel wall;

FIG. 24 shows a plot illustrating the first occurrence of fracture afterdilating the stent/scaffold to diameters substantially larger than thenominal/labeled stent/scaffold diameter of 3.0 mm;

FIG. 25A depicts a scaffold (another name for a stent) at 3.0 mmnominal/labeled diameter, FIG. 25B depicts a scaffold deployed atnominal and further balloon expanded to about 3.8 mm without fracture,FIG. 25C depicts a scaffold deployed at nominal and further balloonexpanded to about 4.0 mm without fracture, FIG. 25D depicts a scaffolddeployed at nominal and further balloon expanded to 4.4 mm diameterwithout fracture, FIG. 25E depicts a scaffold deployed at about nominaland further balloon expanded to about 4.75 mm diameter without fracture,and FIG. 25F depicts a scaffold deployed at about nominal or labeled 3.0mm and further balloon expanded to about 5.1 mm diameter withoutfracture;

FIGS. 26A and 26B depict the DESolve™ Bioresorbable Coronary StentScaffold used in the DESolve 1 clinical trial;

FIG. 27 depicts preclinical optical coherence tomography (OCT) images ofthe scaffold at different time points;

FIG. 28 schematically depicts the DESolve™ First-in-Man (FIM) studydesign;

FIG. 29 depicts Intravascular Ultrasound (IVUS) results from theDESolve™ FIM study;

FIG. 30 depicts the methodology of OCT analysis where NIH stands forneointimal hyperplasia;

FIG. 31 is a block diagram illustrating the principal steps of themethods of the present invention in one embodiment;

FIGS. 32A and 32B illustrate an exemplary stent structure which may befabricated using the methods of the present invention;

FIG. 33 illustrates the stent of FIGS. 32A and 32B in a radiallyexpanded configuration; and

FIG. 34 illustrates a stent pattern utilized in an Example of thepresent application.

FIG. 35 illustrates a pharmacokinetic release profile of novolimus froma stent demonstrating that over 85% of the drug released in one monthand that a therapeutic tissue drug concentration of 0.5 ng/mg at 90days.

FIG. 36 shows a percent diameter stenosis of the novolimus-stent treatedblood vessel measured by quantitative coronary angiography (QCA) overtwo years.

FIG. 37 provides optical coherence tomography (OCT) images of thenovolimus-stent treated blood vessel measured by quantitative coronaryangiography (QCA) over two years.

FIG. 38 is a graph of the external scaffold area luminal areas derivedfrom the OCT images of FIG. 37.

FIGS. 39 and 40 show a histopathology analysis of alcain blue stainedthe novolimus-stent treated blood vessel. FIG. 39 shows slides at 28days, six months, and two years. FIG. 40 shows slides at nine months.

FIG. 41 shows 6 m diabetes subset QCA outcomes.

FIGS. 42 and 43 show serial IVUS outcomes at baseline (post procedure)and at 6 m: (N=40).

FIG. 44 shows vessel, scaffold, and lumen areas and volumes.

FIG. 45 shows the distribution of % NIH obstruction.

FIG. 46 shows serial OCT outcomes at (scaffold and lumen area) baseline(post-procedure) and at 6 m: (N=38).

FIG. 47 is a series of IVUS/OCT images which provide a lumen areacomparison analysis.

FIG. 48 provides a graphical lumen area comparison analysis.

Table 29 provides an incomplete scaffold apposition (ISA) analysis.

FIGS. 49 and 50 provide an NIH quantification by OCT.

FIGS. 51 and 52 provide an NIH thickness and distribution analysis.

FIGS. 53 and 54 provide a strut coverage (safety surrogate) analysis.

DETAILED DESCRIPTION OF THE INVENTION

In preferred embodiments, improved biodegradable endoprostheses andmethods for their fabrication are provided. The stent prostheses may beformed from one or more amorphous, semi-crystalline, or crystallinebiodegradable polymers.

In some embodiments of the invention, the polymers are modified ortreated to introduce a desired degree of crystallinity. In otherembodiments, introducing crystallinity into the polymer increases thestrength of the polymer so that it is suitable for use as anendoprosthesis and in some cases without substantially lengthening theperiod of biodegradation after implantation. In other embodiments, thepolymeric material is treated to achieve a desired degree ofcrystallinity. In other embodiments, the polymeric material is treatedto control crystallinity.

Some embodiments of the disclosure relate to a biodegradable implantabledevice comprising a body comprising a material which comprises abiodegradable copolymer or polymer blend or mixture. It is appreciatedthat any copolymer or polymer blends or mixture described herein can beformed from one, two, three, four or more different monomers orpolymers, where each of the monomers or polymers comprising thecopolymer or the polymer can be in any amount (e.g., about 0.1% to about99.9%, or about 0.5% to about 99.5%, or about 1% to about 99%, or about2% to about 98%, by weight or molarity).

The substantially amorphous or semi-crystalline polymeric material orthe tubular body formed there from can be modified to controlcrystallinity (e.g., degree of crystallinity) of the polymeric material.In certain embodiments, the substantially amorphous or semi-crystallinepolymeric material or the tubular body formed therefrom undergoes amodification treatment to introduce a desired degree of crystallinityinto the polymeric material to increase the strength of the polymericmaterial without substantially lengthening its degradation time.

Additional embodiments of the disclosure relate to biodegradableendoprostheses (e.g., stents) formed at least partially from asubstantially amorphous, biodegradable polymer, and to biodegradableendoprostheses comprising a tubular body formed at least partially froma substantially amorphous, biodegradable polymer. In some embodiments,the biodegradable endoprostheses are comprised of a material whichcomprises a biodegradable polymer, or the biodegradable endoprosthesescomprise a tubular body comprised of a material which comprises abiodegradable polymer, wherein the material or the polymer issubstantially amorphous or semi-crystalline prior to a modification (ortreatment), and crystallinity (e.g., degree of crystallinity) of thematerial or the polymer increases after the material, the polymer, thetubular body, or the endoprosthesis undergoes the modification. In oneembodiment, the crystallinity increases by about 1% to about 40%, or byabout 5% to about to about 35%, or by about 10% to about 30, or by about10% to about 25%, of the original crystallinity prior to modification.In another embodiment, the crystallinity after treatment (modification)is less than about 40%, or less than about 35%, or less than about 30%,or less than about 25%. In one embodiment, the substantially amorphouspolymeric material or semi-crystalline material can decrease the periodof degradation of the endoprosthesis or the tubular body to, e.g., lessthan about four years, or less than about three years, or less thanabout two years, or less than about one year, or less than about ninemonths, or less than about six months, or shorter.

In some embodiments, amorphous biodegradable polymers having less than10% crystallinity can degrade faster than crystalline polymers but areweaker than crystalline polymers and hence are not typically suitablefor vascular implants, such as stents, which need sufficient strength toprovide support to the blood vessel. The present invention provides forthe modification of polymeric materials to make them suitable for use asbiodegradable stents and other endoprostheses. Materials suitable formodification according to the present invention include but are notlimited to poly-DL-Lactide, polylactide-co-glycolactide;polylactide-co-polycaprolactone, poly (L-lactide-co-trimethylenecarbonate), polytrimethylene carbonate and copolymers;polyhydroxybutyrate and copolymers; polyhydroxyvalerate and copolymers,poly orthoesters and copolymers, poly anhydrides and copolymers,polyiminocarbonates and copolymers and the like. An exemplary stent ismade from amorphous material of a copolymer of 85/15Poly(L-Lactide-co-Glycolide) and processed to increase crystallinity byat least 20% of original crystallinity, preferably by at least 100%,more preferably by at least 1000% of original crystallinity. In oneembodiment, the biodegradable stent substantially degrades in less than2 years, preferable less than 1 year, more preferable less than 9months.

In some embodiments, the polymers' crystallinity of the polymericmaterial after modification or treatment is increased by at least 10% ofthe original crystallinity of the polymer material, preferably by atleast 20% of the original crystallinity of the polymer material,preferably by at least 50% of the original crystallinity of the polymermaterial, and more preferably by at least 100% of the originalcrystallinity of the polymer material.

In another embodiment, the initial diameter is 0.9-1.5 times the stentdeployment diameter, or the stent nominal diameter. The stent nominaldiameter is the labeled deployment stent diameter. The stent deploymentdiameter usually is the deployed diameter of the stent at nominal orbigger diameter. In another embodiment, the initial diameter is smallerthan the deployed stent diameter or smaller than the labeled stentdeployed diameter.

In a preferred embodiment, the polymeric material prior to a treatmentis amorphous. In other embodiments, the polymeric material prior to atreatment is semi-crystalline. In a further embodiment, the polymericmaterial prior to a treatment is crystalline.

In certain embodiments, the material (e.g., polymeric material)comprising the body of the device or the biodegradable polymer orcopolymer has a crystallinity or percent crystallinity by X-raydiffraction (XRD) or differential scanning calorimetry (DSC), by weightor volume of about 0%, 1%, 2%, 5% or 10% to about 70%; or about 0%, 1%,2%, 5% or 10% to about 60%; or about 0%, 1%, 2%, 5% or 10% to about 55%;or about 0%, 1%, 2%, 5% or 10% to about 50%; or about 0%, 1%, 2%, 5% or10% to about 40%; or about 0%, 1%, 2%, 5% or 10% to about 30%; or about0%, 1%, 2%, 5% or 10% to about 25%; or about 0%, 1%, 2%, 5% or 10% toabout 20%. In certain embodiments, the material (e.g., polymericmaterial) comprising the body of the device or the biodegradable polymercopolymer has a degree of crystallinity, or % crystallinity by XRD orDSC, of about 5% to about 30%, or about 7% to about 22%, by weight orvolume.

In some embodiments, the amorphous biodegradable polymeric material isprocessed to increase its crystallinity. Increased crystallinity mayincrease the strength, storage shelf life, and hydrolytic stability ofthe polymer stent material. The process initiates and/or enhancescrystallinity in the polymeric material by nucleating and/or growingsmall size spherulite crystals in the material. Since the amorphousregions of the modified polymer in some embodiments are preferentiallybroken down by hydrolysis or enzymatic degradation in biologicalenvironment, the modified amorphous biodegradable polymer in thoseembodiments has increased crystallinity and increased material strengthpost processing. The increase in crystallinity can be achieved bymodifications described in present invention which include at least oneof heating, cooling, pressurizing, addition of additives, crosslinkingand other processes.

The polymer material can be made into a tube by spraying, extrusion,molding, dipping or printing or other process from a selected amorphouscopolymer. The amorphous polymer tubing is optionally vacuumed to atleast −25 in. Hg, annealed, and quenched to increase crystallinity. Inone embodiment, the tube is vacuumed at or below 1 torr at ambienttemperature to remove water and solvent. It is then annealed by heatingto a temperature above the glass transitional temperature but belowmelting temperature of the polymer material. Preferably, the annealingtemperature is at least 10° C. higher than the glass transitionaltemperature (Tg), more preferably being at least 20° C. higher, andstill more preferably being at least 30° C. higher than the Tg. Theannealing temperature is usually at least 5° C. below the melting point(Tm), preferably being at least 20° C. lower, and more preferably beingat least 30° C. lower than the Tm of the polymer material. The annealingtime is between 1 minute to 10 days, preferably from 30 minutes to 3hours, and more preferably from 1.5 hours to 2.5 hours.

In another embodiment, the treatment comprising heating ranges from afraction of a second to seven days, preferably from 30 seconds to 3days, more preferably from 1 minute to 24 hours, and most preferablyfrom 2 minutes to 10 hours.

In one embodiment, the heated (annealed) tube is quenched by fastcooling from the annealing temperature to a temperature at or belowambient temperature over a period from 1 second to 1 hour, preferably 1minute to 30 minutes, and more preferably 5 minutes to 15 minutes. Inanother embodiment the annealed tune is quenched by slow cooling fromthe annealing temperature to at or below ambient temperature within 1hour to 24 hours, preferably 4 hours to 12 hours, and more preferably 6hours to 10 hours. In some instances the heat treated tube is cooled toa temperature below ambient temperature for a period from 1 minute to 96hours, more preferably 24 hours to 72 hours, to stabilize the crystalsand/or terminate crystallization. This annealing and quenching processinitiates and promotes nucleation of crystals in the polymer andincreases the mechanical strength of the material. The initial annealingtemperature and the cooling rate can be controlled to optimize the sizeof the crystals and strength of the material. In a further embodiment,the unannealed and/or annealed tube is exposed to ebeam or gammaradiation, with single or multiple doses of radiation ranging from 5 kGyto 100 kGy, more preferably from 10 kGy to 50 kGy.

In another embodiment, the biodegradable polymeric stent material canhave increased crystallinity by cross-linking such as exposure toradiation such as gamma or ebeam. The cumulative radiation dose canrange from 1 kGy to 1000 KGy, preferably 5 to 100 KGy, more preferably10 to 30 KGy.

Crystallinity (e.g., degree of crystallinity) of the material (e.g.,polymeric material) comprising a polymeric material (e.g., a tube) canbe controlled by exposure of the polymeric article to carbon dioxide gasor liquid, e.g., under conditions used for controlling solvents andmonomers as described herein. When the degree of crystallinity of thepolymeric material comprising the polymeric article is relatively low,exposure of the polymeric material to carbon dioxide gas or liquid cancontrol crystallinity by decrease or increase the degree ofcrystallinity. When the degree of crystallinity of the polymericmaterial is relatively high, exposure of the polymeric article to carbondioxide gas or liquid can potentially decrease the degree ofcrystallinity.

Some embodiments of the disclosure relate to biodegradable implantabledevices (e.g., a stent) comprising a body (e.g., a tubular body)comprising a material which comprises a biodegradable polymer,copolymer, or polymer blend, wherein the material comprising the body,or the biodegradable polymer, copolymer, or polymer blend, or the stent,has a degree of crystallinity of about 0% to about 70%, or of about 0%to about 55%, or of about 0% to about 30%, or of about 0% to about 25%,or of about 5% to about 70%, or of about 5% to about 55%, or of about 5%to about 30%, or of about 5% to about 25%, or of about 10% to about 70%,or of about 10% to about 55%, or of about 10% to about 30%, or of about10% to about 25%; or of about 15% to about 70%, or of about 15% to about55%, or of about 15% to about 30%, or of about 15% to about 25%, or ofabout 0% to about 40%, or of about 0% to about 35%, or of about 0% toabout 25%, or of about 0% to about 20%, or of about 0% to about 15%, orof about 5% to about 40%, or of about 5% to about 35%, or of about 5% toabout 25%, or of about 5% to about 20%, or of about 5% to about 15%, orgreater than 0% to about 10%, or greater than 1% to about 10%; beforemodification or treatment, or after modification or treatment, or with amodification or treatment, or without a modification or treatment, orprior to implant, or after sterilization, or before patterning, or afterpatterning, or the stent, or the tubular body.

In yet another preferred embodiment, the stent or body or biodegradablematerial, is substantially amorphous. In yet another preferredembodiment, the stent or body or biodegradable material, issubstantially amorphous prior to treatment. In yet another preferredembodiment, the stent or body or biodegradable material, issubstantially amorphous prior to treatment and substantially amorphousafter treatment. In yet another preferred embodiment, the stent or bodyor biodegradable material, is substantially amorphous prior to treatmentand substantially semi-crystalline after treatment. In yet anotherembodiment, the stent or tubular body or biodegradable material, hascrystallinity that is higher prior to treatment than the crystallinityafter treatment. In yet another embodiment, the stent or tubular body orbiodegradable material, has crystallinity that is higher prior totreatment than the crystallinity after treatment wherein the stent ortubular body or biodegradable material, is in an amorphous state priorto said treatment. In yet another embodiment, the stent or tubular bodyor biodegradable material, has crystallinity that is substantiallysimilar prior to treatment to the crystallinity after treatment whereinthe stent or tubular body or biodegradable material, is in an amorphousstate prior to said treatment. In yet another embodiment, the stent ortubular body or biodegradable material, has crystallinity of about 0% toabout 50% prior to treatment and has crystallinity of about 0% to about50% after treatment. In yet another embodiment, the stent or tubularbody or biodegradable material, has crystallinity of about 0% to about45% prior to treatment and has crystallinity of about 0% to about 45%after treatment. In yet another embodiment, the stent or tubular body orbiodegradable material, has crystallinity of about 0% to about 40% priorto treatment and has crystallinity of about 0% to about 40% aftertreatment. In yet another embodiment, the stent or tubular body orbiodegradable material, has crystallinity of about 0% to about 35% priorto treatment and has crystallinity of about 0% to about 35% aftertreatment. In yet another embodiment, the stent or tubular body orbiodegradable material, has crystallinity of about 0% to about 35% priorto treatment and has crystallinity of about 0% to about 35% aftertreatment. In yet another embodiment, the stent or tubular body orbiodegradable material, has crystallinity of about 0% to about 30%treatment and has crystallinity of about 0% to about 30% aftertreatment. In yet another embodiment, the stent or tubular body orbiodegradable material, has crystallinity of about 0% to about 25% priorto treatment and has crystallinity of about 0% to about 25% aftertreatment. In yet another embodiment, the stent or tubular body orbiodegradable material, has crystallinity of about 0% to about 20% priorto treatment and has crystallinity of about 0% to about 20% aftertreatment. In yet another embodiment, the stent or tubular body orbiodegradable material, has crystallinity of about 0% to about 15% priorto treatment and has crystallinity of about 0% to about 15% aftertreatment. In yet another embodiment, the stent or tubular body orbiodegradable material, has crystallinity of about 0% to about 25% priorto treatment and has crystallinity of about 0.3% to about 40% aftertreatment. In yet another embodiment, the stent or tubular body orbiodegradable material, has crystallinity of about 0% to about 25% priorto treatment and has crystallinity of about 0% to about 20% aftertreatment. In certain embodiments, the material comprising the body ofthe device or the biodegradable polymer, copolymer or the stent, has adegree of crystallinity of about 5% to about 30% and a T_(g) of about35° C. to about 70° C.

In certain embodiments, the biodegradable copolymer is a polylactidecopolymer, where lactide includes L-lactide, D-lactide and D,L-lactide.In another embodiment, the biodegradable polymer or tubular body orprosthesis comprises a poly-l-lactide acid (PLLA) polymer that issubstantially amorphous or substantially semi crystalline. In anotherembodiment, the biodegradable polymer or tubular body or prosthesiscomprises a PLLA polymer that is substantially amorphous orsubstantially semi crystalline, wherein the tubular body issubstantially randomly oriented, or substantially not oriented, or nonuniformly oriented, or not biaxially oriented. In another embodiment,the biodegradable polymer is PLLA polymer that is substantiallyamorphous or substantially semi crystalline, and/or having a %crystallinity ranging from about 0% to about 30%. In another embodiment,the biodegradable polymer is PLLA polymer that is substantiallyamorphous or substantially semi crystalline, and/or having a %crystallinity ranging from about 0% to about 30% after a modification.In another embodiment, the biodegradable polymer is PLLA polymer that issubstantially amorphous before and after modification. In anotherembodiment, the biodegradable polymer is PLLA polymer that issubstantially amorphous before modification and semi crystalline aftermodification. In another embodiment, the biodegradable polymer is PLLApolymer that is substantially semi crystalline before modification andcrystalline after modification. In another embodiment, the biodegradablepolymer is PLLA polymer that is substantially amorphous or substantiallysemi crystalline and/or having a % crystallinity ranging from about 0%to about 30% after a modification and/or having % elongation orshrinkage of about 10% to about 50% after treatment; or of less than 10%after treatment. In another embodiment, the biodegradable polymer isPLLA polymer that is substantially amorphous or substantially semicrystalline, and/or having a % crystallinity ranging from about 0% toabout 30% after a modification, and/or having % elongation or shrinkageof about 10% to about 50% after treatment, and/or capable of radialexpansion from a crimped state to an expanded state in an aqueousenvironment at about 37° C. In yet another embodiment, variouscombinations of the embodiments are included.

In another embodiment, it is desired to control crystallinity in amanner to preserve the material properties after forming. For example itis desirable to treat the tubular body or the biodegradable polymericmaterial wherein the crystallinity of the tubular body after forming issubstantially unchanged from the crystallinity of the stent prosthesismaterial prior to implant. In such cases, the treatment(s) of thebiodegradable polymeric material controls maintaining crystallinity tobe substantially the same.

In another embodiment, it is desired to control crystallinity in amanner to lower crystallinity after forming or after treatment. Forexample it is desirable to treat the tubular body or the biodegradablepolymeric material wherein the crystallinity of the stent prosthesismaterial prior to implant is lower than the crystallinity of the tubularbody after forming.

The biodegradable stent prosthesis comprising a tubular body comprisinga biodegradable polymeric material, wherein the tubular body has beenformed using extrusion, molding, dipping, or spraying, saidbiodegradable polymeric material has an initial crystallinity and has aTg greater than 37° C. and the stent prosthesis has a crystallinity(biodegradable stent material) that is substantially the same as theinitial crystallinity and at body temperature is radially expandable andhas sufficient strength to support a body lumen.

In certain embodiments, the material (e.g., polymeric material)comprising the body of the device or the biodegradable polymer orcopolymer has a crystallinity or percent crystallinity by X-raydiffraction (XRD) or differential scanning calorimetry (DSC), by weightor volume of about 0%, 1%, 2%, 5% or 10% to about 70%; or about 0%, 1%,2%, 5% or 10% to about 60%; or about 0%, 1%, 2%, 5% or 10% to about 55%;or about 0%, 1%, 2%, 5% or 10% to about 50%; or about 0%, 1%, 2%, 5% or10% to about 40%; or about 0%, 1%, 2%, 5% or 10% to about 30%; or about0%, 1%, 2%, 5% or 10% to about 25%; or about 0%, 1%, 2%, 5% or 10% toabout 20%. In certain embodiments, the material (e.g., polymericmaterial) comprising the body of the device or the biodegradable polymercopolymer has a degree of crystallinity, or % crystallinity by XRD orDSC, of about 5% to about 30%, or about 7% to about 22%, by weight orvolume.

In a preferred embodiment, there is a desire to minimize the amount ofheat and/or duration the tubular body or the stent or the biodegradablematerial sees after forming. Examples include treating the tubular bodyby heating the tubular body after forming to temperature at about Tg orlower than Tg or within 10° C. higher than Tg, of the biodegradablepolymeric material Tg, for duration ranging from a fraction of a secondto 7 days, or 5 seconds to 7 days, preferably from 15 seconds to 1 day,more preferably from 30 seconds to 5 hours, and optionally cooling orquenching after heating to above ambient temperature, ambienttemperature or below ambient temperature. The heating can take placeonce or more than once at various stages of the tubular body or stentprosthesis fabrication. In one embodiment, the biodegradable stentprosthesis comprising a tubular body comprising a biodegradablepolymeric material, wherein the tubular body has been formed usingextrusion, molding, dipping, or spraying and has been treated by heatingthe tubular body at about Tg or lower of the biodegradable polymericmaterial Tg, said biodegradable polymeric material is substantiallyamorphous after said treatment and has a Tg greater than 37° C. and thestent prosthesis at body temperature is radially expandable and hassufficient strength to support a body lumen. In another embodiment, thebiodegradable stent prosthesis comprising a tubular body comprising abiodegradable polymeric material, wherein the tubular body has beenformed using extrusion, molding, printing, dipping, or spraying and hasbeen treated by heating the tubular body at about Tg or lower of thebiodegradable polymeric material Tg, said biodegradable polymericmaterial has crystallinity of 10%-60% (or 10%-50% or 10%-40% or 10% to30% or 10%-20% or 0%-10% or 0% to 30%) after said treatment and has a Tggreater than 37° C. and the stent prosthesis at body temperature isradially expandable and has sufficient strength to support a body lumen.In one embodiment, the Tg is greater than 37° C. and less than 60° C.,preferably greater than 37° C. and less than 55° C., more preferablygreater than 37° C. and less than 45° C., more preferably greater than35° C. and less than 45° C.

In certain embodiments, the degree of crystallinity is controlled in thepolymeric material to about 40% or less, or about 35% or less, or about30% or less, or about 25% or less, or about 20% or less, or about 15% orless, or about 10% or less, or about 8% or less, or about 6% or less, orabout 4% or less, or about 2% or less, prior to a modification (ortreatment) or after modification. In an embodiment, the degree ofcrystallinity of a polymeric material is about 10% or less prior to amodification.

In some embodiments, after a substantially amorphous or semi crystallineor crystalline polymeric material or a tubular body formed therefromundergoes a modification, the degree of crystallinity of the polymericmaterial is controlled such as to increases or decrease by at leastabout 5%, 10%, 20%, 30%, 40%, 50%, 100%, 150%, 200%, 300%, 400%, 500%,600%, 700%, 800%, 900% or 1000% (e.g., of the initial degree ofcrystallinity or before treatment). In an embodiment, after asubstantially amorphous or semi crystalline or crystalline polymericmaterial or a tubular body formed therefrom undergoes a modification,the degree of crystallinity of the polymeric material increases by atleast about 50%.

In further embodiments, polymeric material or a tubular body formedtherefrom undergoes a modification, the polymeric material has a degreeof crystallinity of about 2%, 5% or 10% to about 70%; or about 2%, 5% or10% to about 60%; or about 2%, 5% or 10% to about 50%; or about 2%, 5%or 10% to about 40%; or about 2%, 5% or 10% to about 30%; or about 2%,5% or 10% to about 20%. In an embodiment, the polymeric material or atubular body formed therefrom undergoes a modification, the polymericmaterial has a degree of crystallinity of about 10% to about 40%. Inanother embodiment, the polymer material or tubular body or stentcomprises PLLA/PCL (polymer blend or copolymers), wherein the tubularbody is substantially oriented, or at least axially oriented, orbiaxially oriented, or substantially randomly oriented, or substantiallynot oriented. In another embodiment, the polymer material is PLLA/PCL(polymer blend or copolymers) and an additive of carbon nano tube orfibers are added to it. The amounts of carbon nano tube or fibers rangesfrom about 0.1% to about 15%. In another embodiment, the polymermaterial comprises PLLA/PCL/PGA (polymer blend or copolymers or amixture of copolymers and polymer blend) and an additive of carbon nanotube or fibers added to it. The amounts of carbon nano tube or fibersranges from about 0.1% to about 15%. In some embodiments, crystallinityof the tubular body after modification ranges from about 10% to about70% and % elongation ranges from about 10% to about 200%, and Tg rangesfrom about 35° C. to about 60° C., or a Tg greater than 37° C. to about55° C., or a Tg greater than 37° C. to about 45° C., or a Tg greaterthan 35° C. to about 45° C.

In further embodiments, the material (e.g., polymeric material)comprising the body of an endoprosthesis (e.g., a stent), or comprisingthe polymeric article/material (e.g., a polymeric tube) from which theendoprosthesis is formed, has a degree of crystallinity of about 2%, 5%or 10% to about 70%, or about 2%, 5% or 10% to about 60%, or about 2%,5% or 10% to about 50%, or about 2%, 5% or 10% to about 40%, or about2%, 5% or 10% to about 30%, or about 2%, 5% or 10% to about 20%, or hasa degree of crystallinity of at least about 2%, 5%, 10%, 20%, 25%, 30%,40%, 50%, 60% or 70%, after the polymeric article and/or theendoprosthesis undergo the modification or treatment. In certainembodiments, the material (e.g., polymeric material) comprising thepolymeric article or the body of the endoprosthesis has a degree ofcrystallinity of about 5% to about 50%, or about 10% to about 40%, afterthe polymeric article and/or the endoprosthesis undergo themodification.

Increased crystallinity may increase the strength, storage shelf life,and/or hydrolytic stability of the polymeric material or theendoprosthesis formed therefrom. The modification may introduce orenhance crystallinity in the polymeric material by nucleating or growingsmall spherulite crystals in the polymeric material. Modification of apolymeric material can include longitudinal extension, radial expansion,heating, cooling, pressurizing, vacuuming, addition of an additive,crosslinking, exposure to radiation (e.g., e-beam or gamma radiation),exposure to carbon dioxide gas or liquid, or other modificationsdescribed herein, or a combination thereof.

Additional embodiments of the disclosure relate to biodegradableendoprostheses comprised of a material which comprises a biodegradablepolymer, or biodegradable endoprostheses comprising a tubular bodycomprised of a material which comprises a biodegradable polymer, whereinthe material or the polymer is substantially amorphous or semicrystalline or crystalline prior to a modification (or treatment), andcrystallinity (e.g., degree of crystallinity) of the material or thepolymer increases or decreases after the material, the polymer, thetubular body or the endoprosthesis undergoes the modification. In oneembodiment, the crystallinity increases or decreases from about 1% toabout 30%, in another embodiment, the crystallinity increases from about1% to about 20%, or from about 1% to about 10%, or no more than 10%.

Substantially amorphous or semi-crystalline, biodegradable polymershaving a degree of crystallinity of, e.g., about 30% or less, or 20% orless, or 10% or less may degrade faster than crystalline polymers. Thepresent disclosure provides for modifications (or treatments) ofpolymers, preferably substantially amorphous or semi crystallinepolymeric materials to increase crystallinity of biodegradableendoprostheses, e.g., or by increasing the strength of the polymericmaterial without substantially increasing its degradation time. Incertain embodiments, a biodegradable endoprosthesis (e.g., a stent)formed from a substantially amorphous or semi crystalline polymericmaterial that has undergone a modification substantially completelydegrades in less than about four years, or less than about three years,or less than about two years, or less than about one year, or less thanabout nine months, or less than about six months.

In some embodiments, a biodegradable endoprosthesis (e.g., a stent) isformed from a biodegradable polymeric material, wherein crystallinity(e.g., degree of crystallinity) of the polymeric material is controlledby increasing or decreasing after the polymeric material undergoes amodification (or treatment). In certain embodiments, the degree ofcrystallinity of the polymeric material increases or decreases by atleast about 10%, 20%, 25%, 30%, 40%, 50%, 75%, 100%, 150%, 200%, 300%,400%, 500%, 600%, 700%, 800%, 900% or 1000% after the polymeric materialundergoes the modification. In certain embodiments, the degree ofcrystallinity of polymeric material increases by at least about 25% or50% after the polymeric material undergoes the modification.

In one embodiment, the biodegradable polymeric stent material hasincreased crystallinity by using a combination of solvents, with onesolvent having solubility parameter within 10% of the solubilityparameter of the polymer and the second solvent having solubilityparameter at least 10% different than the solubility parameter of thepolymer in the solvent.

In one embodiment the biodegradable polymer stent material has acrystallinity of greater than 10%, preferably greater than 25%, morepreferably greater than 50%. In other embodiments, treatment to controlcrystallinity takes place in such a way as to decrease it aftertreatment. Examples include decreasing the crystallinity by at least5%-50%, preferably by at least 10% to 30%.

In some embodiments, the invention also provides means to improveconsistency of strength, recoil or degradation rate of a biodegradablepolymer stent material.

Another way to control crystallinity of the material (e.g., polymericmaterial) comprising the body of an endoprosthesis (e.g., a stent), orcomprising the polymeric article/material (e.g., a tube) from which theendoprosthesis is formed, is to use a combination of solvents in whichthe polymeric material has different solubilities (e.g., when thepolymeric article is being formed). For example, one solvent can have asolubility parameter within about 20% (or 10%) of the solubilityparameter of the polymeric material, and the second solvent can have asolubility parameter at least about 20% (or 10%) different than thesolubility parameter of the polymeric material in the solvent.

In some embodiments, the first biodegradable polymer or the material(e.g., polymeric material) comprising the polymeric article or the bodyof the device has a degree of crystallinity, or percent crystallinity byX-ray diffraction (XRD) or differential scanning calorimetry (DSC), ofabout 20%, 15%, 10% or 5% or less by weight or volume before thepolymeric article or the device undergoes a treatment (e.g., heating orexposure to radiation), and the degree of crystallinity, or %crystallinity by XRD or DSC, of the first biodegradable polymer or thematerial (e.g., polymeric material) comprising the polymeric article orthe body of the device increases by at least about 10%, 20%, 30%, 40%,50%, 100%, 200%, 300%, 400% or 500% after the polymeric article or thedevice undergoes the treatment. In certain embodiments, the firstbiodegradable polymer or the material (e.g., polymeric material)comprising the polymeric article or the body of the device has a degreeof crystallinity, or % crystallinity by XRD or DSC, of about 15% or lessby weight or volume before the polymeric article or the device undergoesa treatment (e.g., heating or exposure to radiation), and the degree ofcrystallinity, or % crystallinity by XRD or DSC, of the firstbiodegradable polymer or the material (e.g., polymeric material)comprising the polymeric article or the body of the device increases byat least about 20% after the polymeric article or the device undergoesthe treatment.

In further embodiments, the first biodegradable polymer or the material(e.g., polymeric material) comprising the polymeric article or the bodyof the device has a degree of crystallinity, or % crystallinity by XRDor DSC, of about 20%, 15%, 10% or 5% or less by weight or volume beforethe polymeric article or the device undergoes a treatment (e.g., heatingor exposure to radiation), and the first biodegradable polymer or thematerial (e.g., polymeric material) comprising the polymeric article orthe body of the device has a degree of crystallinity, or % crystallinityby XRD or DSC, by weight or volume of about 2%, 5% or 10% to about 70%,or about 2%, 5% or 10% to about 60%, or about 2%, 5% or 10% to about50%, or about 2%, 5% or 10% to about 40%, or about 2%, 5% or 10% toabout 30%, or about 2%, 5% or 10% to about 20%, after the polymericarticle or the device undergoes the treatment. In certain embodiments,the first biodegradable polymer or the material (e.g., polymericmaterial) comprising the polymeric article or the body of the device hasa degree of crystallinity, or % crystallinity by XRD or DSC, of about15% or less by weight or volume before the polymeric article or thedevice undergoes a treatment (e.g., heating or exposure to radiation),and the first biodegradable polymer or the material (e.g., polymericmaterial) comprising the polymeric article or the body of the device hasa degree of crystallinity, or % crystallinity by XRD or DSC, of about10% to about 50% by weight or volume after the polymeric article or thedevice undergoes the treatment.

In yet further embodiments, the first biodegradable polymer or thematerial (e.g., polymeric material) comprising the polymeric article orthe body of the device has a degree of crystallinity, or % crystallinityby XRD or DSC, of about 15% or less, or about 10% or less, by weight orvolume before the polymeric article or the device is exposed toradiation (e.g., e-beam or gamma radiation), and the first biodegradablepolymer or the material (e.g., polymeric material) comprising thepolymeric article or the body of the device has a degree ofcrystallinity, or % crystallinity by XRD or DSC, of about 10% to about40%, or about 10% to about 30%, or about 10% to about 20%, by weight orvolume after the polymeric article or the device is exposed to theradiation. In certain embodiments, the first biodegradable polymer orthe material (e.g., polymeric material) comprising the polymeric articleor the body of the device has a degree of crystallinity, or %crystallinity by XRD or DSC, of about 10% or less by weight or volumebefore the polymeric article or the device is exposed to radiation(e.g., e-beam or gamma radiation), and the first biodegradable polymeror the material (e.g., polymeric material) comprising the polymericarticle or the body of the device has a degree of crystallinity, or %crystallinity by XRD or DSC, of about 10% to about 30% by weight orvolume after the polymeric article or the device is exposed to theradiation.

In still further embodiments, the first biodegradable polymer or thematerial (e.g., polymeric material) comprising the polymeric article hasa degree of crystallinity, or % crystallinity by XRD or DSC, of about15% or less, or about 10% or less, by weight or volume before the deviceis formed from the polymeric article (e.g., by laser or mechanicalcutting), and the first biodegradable polymer or the material (e.g.,polymeric material) comprising the body of the device has a degree ofcrystallinity, or % crystallinity by XRD or DSC, of about 10% to about40%, or about 10% to about 30%, or about 10% to about 20%, by weight orvolume after the device undergoes a treatment (e.g., heating or exposureto radiation). In certain embodiments, the first biodegradable polymeror the material (e.g., polymeric material) comprising the polymericarticle has a degree of crystallinity, or % crystallinity by XRD or DSC,of about 10% or less by weight or volume before the device is formedfrom the polymeric article (e.g., by laser or mechanical cutting), andthe first biodegradable polymer or the material (e.g., polymericmaterial) comprising the body of the device has a degree ofcrystallinity, or % crystallinity by XRD or DSC, of about 10% to about30% by weight or volume after the device undergoes a treatment (e.g.,heating or exposure to radiation).

In additional embodiments, the first biodegradable polymer or thematerial (e.g., polymeric material) comprising the polymeric article orthe body of the device has a degree of crystallinity, or % crystallinityby XRD or DSC, by weight or volume of about 2%, 5% or 10% to about 70%,or about 2%, 5% or 10% to about 60%, or about 2%, 5% or 10% to about55%, or about 2%, 5% or 10% to about 50%, or about 2%, 5% or 10% toabout 40%, or about 2%, 5% or 10% to about 30%, or about 2%, 5% or 10%to about 25%, or about 2%, 5% or 10% to about 20%, or about 7% to about22%, before and/or after the polymeric article or the device undergoes atreatment (e.g., heating or exposure to radiation). In certainembodiments, the first biodegradable polymer or the material (e.g.,polymeric material) comprising the polymeric article or the body of thedevice has a degree of crystallinity, or % crystallinity by XRD or DSC,of about 5% to about 30%, or about 10% to about 25%, or about 7% toabout 22%, by weight or volume after the polymeric article or the deviceundergoes a treatment (e.g., heating or exposure to radiation).

The teachings disclosed herein can be applied to make any appropriateimplantable device from a polymeric article comprised of a biodegradablepolymeric material. The implantable device can be any implantable devicedescribed herein, and may have a tubular body (e.g., a stent) or may nothave a tubular body. The polymeric article can have any shape, form anddimensions suitable for making the device (e.g., a polymeric tube fromwhich a stent is patterned).

In another aspect of the invention, methods for fabricatingbiodegradable prostheses are provided. The preferred methods compriseproviding a tubular body having an initial diameter as-formed, or beforepatterning, or after patterning, where the tubular body comprises abiodegradable polymeric material. In one embodiment, the polymericmaterial comprises one or more polymers, or one or more co-polymers, ora combination thereof. In another embodiment, the polymeric materialcomprises one or more polymers, or one or more co-polymers, or one ormore monomers, or a combination thereof. The polymeric material or thetubular body is treated to control crystallinity preferably to between1% and 50%, or more preferably to between 1% and 35%. In one embodimentthe polymeric material or the tubular body treatment comprises a heattreatment preferably at substantially the initial diameter, preferablywhen the initial diameter is 1-1.5 times the stent deployment diameter,to a temperature above glass transition temperature of the polymericmaterial and below its melting point for a period ranging from afraction of a second to 7 days. The polymeric material or the tubularbody in one embodiment may be cooled after heating to a temperatureranging from below ambient temperature to ambient or above temperatureover a period ranging from a fraction of a second to 7 days. In apreferred embodiment, the polymeric material or the tubular body initialdiameter is approximately 1-1.5 times the stent deployment diameter orstent nominal deployment diameter, or stent labeled deployment diameter.In another preferred embodiment, the initial diameter is approximately0.9-1.5 times the stent deployment diameter or stent nominal deploymentdiameter, or stent labeled deployment diameter.

The biodegradable implantable device can be made using any suitablemethod, such as spraying, dipping, extrusion, molding, injectionmolding, compression molding or 3-D printing, using, e.g., BFB3000 fromBits From Bytes company (UK), or a combination thereof. In someembodiments, the body of the device is formed from a polymeric articlemade by spraying a solution or mixture containing the biodegradablecopolymer or polymer and a solvent onto a structure. In a preferredembodiment, the biodegradable stent is fabricated by forming a tubularbody using extrusion, molding such as injection molding, dipping,spraying such as spraying a tube or mandrel, printing such as 3Dprinting. The tubular body in a preferred embodiment is formed first andthen patterned into a structure capable of radial expansion from acrimped configuration preferably at body temperature. The tubular bodyin another preferred embodiment is formed first and then patterned intoa structure capable of radial expansion from a crimped configurationpreferably at body temperature and preferably without fracture. Thetubular body in another preferred embodiment is formed first and thenpatterned into a structure capable of being crimped from an expandedconfiguration to a crimped diameter (at temperature about Tg or lessthan Tg), and at body temperature capable to be expanded from thecrimped configuration preferably without fracture. In another preferredembodiment the polymeric material is patterned first and then forms atubular body/stent capable of radial expansion at body temperatureand/or capable to be crimped preferably at temperature about Tg or lessthan Tg.

In certain embodiments, the tubular body or polymeric material, or thestent has an initial diameter. In one preferred embodiment, the initialdiameter is 1-1.5 times the stent deployed diameter. In anotherpreferred embodiment, the initial diameter is 0.9-1.5 times the stentdeployed diameter. In a further embodiment, the initial diameter is lessthan the stent deployed diameter. The initial diameter can be theas-formed diameter, or the diameter before patterning, or the diameterafter patterning, or the diameter before crimping. In one embodiment, anendoprosthesis (e.g., a stent) is patterned by laser cutting or othermethod from a polymeric tube that has a (e.g., inner or outer) diametersubstantially equal to or smaller than deployed (e.g., inner or outer)diameter of the endoprosthesis. In other embodiments, an endoprosthesis(e.g., a stent) is patterned from a polymeric tube that has a (e.g.,inner or outer) diameter, either when the tube is formed or after thetube is radially expanded to a second larger diameter, larger thandeployed (e.g., inner or outer) diameter of the endoprosthesis.Patterning a stent from a polymeric tube having a (e.g., inner or outer)diameter larger than deployed (e.g., inner or outer) diameter of thestent can impart advantageous characteristics to the stent, such asreducing radially inward recoil of the stent after deployment and/orimproved strength.

In a preferred embodiment, a stent prosthesis or tubular body orpolymeric material has initial diameter (or initial transversedimension), preferably 1-1.5 times deployed diameter (deployedtransverse dimension) or deployed nominal diameter (e.g., deployednominal transverse dimension), where in the initial diameter (or initialtransverse dimension) is as-formed diameter (or transverse dimension),before patterning diameter (or transverse dimension), or afterpatterning diameter (or transverse dimension), or before crimpingdiameter (or transverse dimension), and wherein the initial diameter (orinitial transverse dimension) is greater than crimped diameter (orcrimped transverse dimension). In a preferred embodiment, a stent ortubular body first self-expands by at least 0.35 of initial diameter ortransverse dimension, and then expands to second larger diameter ortransverse dimension, which may be the deployed diameter or transversedimension, preferably by balloon expansion. In a further preferredembodiment, the stent or tubular body may expand to 1.0 times or more,or 1.1 times or more, or 1.2 times or more, or 1.3 times or more, or 1.4times or more, or 1.5 times or more the deployed diameter or nominaldiameter (or transverse dimension) at body temperature, withoutfracturing. In a further preferred embodiment, the stent or tubular bodyor polymeric material is crimped from an expanded diameter to a crimpedconfiguration, and at body temperature expands to 1.0 times or more, or1.1 times or more, or 1.2 times or more, or 1.3 times or more, or 1.4times or more, or 1.5 times or more the deployed diameter or nominaldiameter (or transverse dimension), without fracturing.

In some embodiments, an expandable stent comprising a biodegradablepolymeric material having an initial configuration is provided. Theexpandable stent at body temperature can be self-expandable from acrimped configuration and further expandable to a second largerconfiguration. In further embodiments, the polymeric material has beentreated to control one or more of crystallinity, Tg, or molecularweight. In some embodiments, the Tg ranges from about 20° C. to about50° C. In some embodiments, the second configuration is a deployedconfiguration. In some embodiments, the stent expands to the first andsecond configurations without fracture and has sufficient strength tosupport a body lumen. In some embodiments, the first expandedconfiguration has a transverse dimension of at least 0.35 times, or atleast 0.45 times, or at least 0.55 times, or at least 0.55 times, or atleast 0.7 times, or at least 0.8 times, or at least 1 times thetransverse dimension of the initial configuration. In some embodiments,the stent expands to the first expanded configuration within a period of24 hours, or 12 hours, or 4 hours, or 2 hours, or 1 hour, or 30 minutes,or 5 minutes or 30 seconds. In some embodiments, the stent is balloonexpandable to the second expanded configuration without fracture andwith sufficient strength to support a body lumen.

In some embodiments, an expandable stent comprising a biodegradablepolymeric material having an initial configuration is provided. Theexpandable stent at body temperature can be expandable from a crimpedconfiguration to a first expanded configuration and self expandable to asecond larger configuration. In further embodiments, the polymericmaterial is treated to control one or more of crystallinity, Tg, ormolecular weight. In some embodiments, the expandable stent comprises asubstantially continuous tubular body. In some embodiments, the stentexpands to the first configuration without fracture and has sufficientstrength to support a body lumen. In some embodiments, the stent has anominal expanded configuration with a transverse dimension and the firstexpanded configuration has a transverse dimension that is at least 1times the transverse dimension of the transverse dimension of thenominal expanded configuration. In some embodiments, the first expandedconfiguration is a deployed configuration. In some embodiments, thestent has a nominal expanded configuration with a transverse dimensionand the first expanded configuration has a transverse dimension that is1 time, or 1.1 times, or 1.2 times, or 1.3 times, or 1.35 times, or 1.4times, or 1.45 times, or 1.5 times the transverse dimension of thetransverse dimension of the nominal expanded configuration.

In certain embodiments, the body of the biodegradable implantable deviceis formed from a polymeric article made by:

(i) spraying a solution or mixture containing the biodegradablecopolymer or polymer and a solvent onto a structure to form a firstlayer containing the biodegradable copolymer or polymer, and

spraying a solution or mixture containing a second biodegradable polymerand a solvent over at least a portion of the first layer containing thebiodegradable copolymer or polymer to form a second layer containing thesecond biodegradable polymer; or

(ii) spraying a solution or mixture containing a second biodegradablepolymer and a solvent onto a structure to form a first layer containingthe second biodegradable polymer, and

spraying a solution or mixture containing the biodegradable copolymer orpolymer and a solvent over at least a portion of the first layercontaining the second biodegradable polymer to form a second layercontaining the biodegradable copolymer. The polymer, copolymers, and/orsolvents can be the same or different for the first and second layers.

In some embodiments, the solution or mixture containing thebiodegradable copolymer contains an additional biodegradable polymer ora non-degradable polymer or both. In certain embodiments, the solutionor mixture containing the biodegradable copolymer contains one or morebiologically active agents, or one or more additives, or bothbiologically active agent(s) and additive(s).

In further embodiments, the solution or mixture containing the secondbiodegradable polymer contains an additional biodegradable polymer or anon-degradable polymer or both. In certain embodiments, the solution ormixture containing the second biodegradable polymer contains one or morebiologically active agents, or one or more additives, or bothbiologically active agent(s) and additive(s).

In additional embodiments, the biodegradable copolymer contains about 5,4, 3, 2, 1, 0.5 or 0.1 wt % or less of each of water, solvent(s),monomer(s), low molecular weight oligomer(s) or particulate(s), or acombination thereof, prior to preparation of the solution or mixturecontaining the biodegradable copolymer, or after spraying of thesolution or mixture, or both. In further embodiments, the secondbiodegradable polymer contains about 5, 4, 3, 2, 1, 0.5 or 0.1 wt % orless of each of water, solvent(s), monomer(s), low molecular weightoligomer(s) or particulate(s), or a combination thereof, prior topreparation of the solution or mixture containing the secondbiodegradable polymer, or after spraying of the solution or mixture, orboth. Low content of water, solvent(s), monomer(s), low molecular weightoligomer(s) or particulate(s), or a combination thereof, in a polymericmaterial can be achieved by methods described herein.

The biodegradable implantable devices described herein can be made usingany suitable method or technique, including without limitation spraying,dipping, extrusion, molding, injection molding, compression molding or3-D printing, or a combination thereof.

Some embodiments of the present disclosure relate to a method of makinga biodegradable implantable device comprising a body comprised of amaterial which comprises a first biodegradable polymer, the methodcomprising:

spraying a first solution or mixture containing the first biodegradablepolymer and a first solvent onto a structure to form a polymericarticle;

optionally removing the polymeric article from the structure; and

forming the implantable device from the polymeric article.

In certain embodiments, the polymer solution or mixture is sprayed ontothe structure at ambient temperature. In other embodiments, the polymersolution or mixture is sprayed onto the structure at a temperature belowor above ambient temperature. In further embodiments, the polymersolution or mixture is sprayed onto the structure in ambientenvironment. In other embodiments, the polymer solution or mixture issprayed onto the structure in a substantially inert environment (e.g.,in the presence of nitrogen or argon gas). In additional embodiments,the polymer solution or mixture is sprayed onto the structure in anenvironment having a relative humidity of about 70% or less, or about60% or less, or about 50% or less, or about 40% or less, or about 30% orless. In certain embodiments, the polymer solution or mixture is sprayedonto the structure in an environment having a relative humidity of about50% or less.

The first biodegradable polymer can be any biodegradable polymer(including homopolymer or copolymer) described herein. In someembodiments, the first biodegradable polymer is a polylactidehomopolymer or copolymer, wherein lactide includes L-lactide, D-lactideand D,L-lactide. In certain embodiments, the first biodegradable polymeris a poly(L-lactide) copolymer. The poly(L-lactide) copolymer cancomprise L-lactide and one or more other monomers selected from any ofthe monomers described herein. In some embodiments, the biodegradablepoly(L-lactide) copolymer comprises L-lactide in at least about 70%,75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% by weight ormolarity, and each of the one or more other monomers in no more thanabout 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%,8%, 9%, 10%, 15%, 20%, 25% or 30% by weight or molarity. In certainembodiments, the biodegradable poly(L-lactide) copolymer comprisesL-lactide in at least about 90%, 95% or 99% by weight or molarity, andeach of the one or more other monomers in no more than about 1%, 5% or10% by weight or molarity.

In certain embodiments, the first biodegradable polymer is selected fromthe group consisting of poly(L-lactide), poly(D-lactide),poly(D,L-lactide), polydioxanone, poly(4-hydroxybutyrate),polysalicylate/polysalicylic acid, poly(propylene carbonate),poly(tyrosine carbonate), poly(cellulose acetate butyrate),poly(L-lactide-co-D-lactide), poly(L-lactide-co-D,L-lactide),poly(L-lactide-co-glycolide), poly(L-lactide-co-ε-caprolactone),poly(L-lactide-co-dioxanone), poly(L-lactide-co-3-hydroxybutyrate),poly(L-lactide-co-4-hydroxybutyrate),poly(L-lactide-co-4-hydroxyvalerate), poly(L-lactide-co-ethylenecarbonate), poly(L-lactide-co-propylene carbonate),poly(L-lactide-co-trimethylene carbonate), andpoly(L-lactide-co-cellulose acetate butyrate).

In further embodiments, the first biodegradable polymer is a block orrandom copolymer of L-lactide and ε-caprolactone in a weight or molarratio of about 70:30 to about 99.9:0.1, or about 80:20 to about99.9:0.1, or about 85:15 to about 99.9:0.1, or about 85:15 to about95:5, or about 87:13 to about 93:7, or about 90:10. In an embodiment,the first biodegradable polymer is a random copolymer of L-lactide andε-caprolactone in a weight or molar ratio of about 90:10. In otherembodiments, the first biodegradable polymer is a block or randomcopolymer of L-lactide and glycolide in a weight or molar ratio of about70:30 to about 99.9:0.1, or about 75:25 to about 95:5, or about 80:20 toabout 90:10, or about 82:18 to about 88:12, or about 85:15. In anembodiment, the first biodegradable polymer is a random copolymer ofL-lactide and glycolide in a weight or molar ratio of about 85:15.

The first solvent can be any solvent (a single solvent or a mixture ofsolvents) that dissolves to a suitable extent, and is compatible with,the first biodegradable polymer and any additional material (e.g., anadditional polymer, a biologically active agent or an additive, or acombination thereof) in the first solution or mixture, and results insuitable characteristics of the polymeric article (e.g., minimal amountof residual solvent after removal of the solvent, if desired).Non-limiting examples of solvents include hydrocarbon solvents, toluene,xylenes, 1,2-xylene, 1,3-xylene, 1,4-xylene, halogenated hydrocarbonsolvents, dichloromethane, chloroform, trichlorofluoromethane,(1,1,1,3,3,3)-hexafluoro-2-propanol, ethers, diethyl ether, methyltert-butyl ether, tetrahydrofuran, ketones, acetone, esters, ethylacetate, tert-butyl acetate, alcohols, methanol, ethanol, isopropanol,tert-butanol, amines, diethylamine, and mixtures thereof. In certainembodiments, the first solvent is dichloromethane, or tetrahydrofuran,or acetone.

The choice of concentration of a polymer in a spray solution or mixturemay be based on various factors, such as the viscosity of the polymer,the type of solvent and the type of spray equipment used. Examples ofspray equipments that can be used include, but are not limited to,MicroMist sprayers from Sono-Tek (New York) and 784S-SS Aseptic sprayersfrom EFD (Rhode Island). In some embodiments, the concentration of thefirst biodegradable polymer in the first solution or mixture is about0.1 or 1 mg/mL to about 20 mg/mL, or about 0.5 or 1 mg/mL to about 15mg/mL, or about 1 or 2 mg/mL to about 10 mg/mL, or about 3 mg/mL toabout 7 mg/mL, or about 4 mg/mL to about 6 mg/mL. In certainembodiments, the concentration of the first biodegradable polymer in thefirst solution or mixture is about 1 mg/mL to about 10 mg/mL, or about 5mg/mL.

In some embodiments, the structure onto which the polymer solution ormixture is sprayed has a substantially flat surface or a contoursurface, or both. In further embodiments, the structure has an irregularsurface, or a surface having surface features. In certain embodiments,the irregular surface, or the surface having surface features, of thestructure has one or more protrusions, and/or one or more indentations,where the protrusions and/or the indentations can be arranged in aregular or irregular manner on the surface. The protrusions and/or theindentations on the surface of the structure can be formed asindentations and/or protrusions, respectively, on the corresponding(e.g., inner) surface of the polymeric article spray coated on thestructure for any of a variety of purposes. For example, a polymericarticle having indentations and/or protrusions on a surface can be usedto make a device that has a variable thickness along its length, whichcan, e.g., increase its longitudinal flexibility. As another example,indentations and/or protrusions on a surface of a device can promoteendothelialization of the device with the surrounding tissue afterimplantation of the device. As a further example, indentations on asurface of a device can contain one or more biologically active agents,or one or more additives, or both.

The structure onto which the polymer solution or mixture is sprayed canhave any shape, configuration or form suitable for making a polymericarticle. In certain embodiments, the structure is a substantiallycylindrical or tubular structure (e.g., a mandrel, rod, tube orballoon), which can be used to make a polymeric article from which,e.g., a single stent, segmented stent, joined stent or overlap stent canbe patterned. In further embodiments, the structure is a tapered tubularstructure (e.g., a tapered mandrel, rod, tube or balloon), which can beused to make a polymeric article from which, e.g., a tapered stent canbe patterned. In additional embodiments, the structure is asubstantially Y-shaped cylindrical or tubular structure (e.g., asubstantially Y-shaped mandrel, rod or tube), which can be used to makea polymeric article from which, e.g., a bifurcated stent can bepatterned.

Further, the polymeric article can have any shape, configuration or formsuitable for making an implantable device from the polymeric article. Incertain embodiments, the polymeric article is a polymeric sheet. Inother embodiments, the polymeric article is a polymeric tube.

When the polymeric article is a polymeric tube, in some embodiments thepolymeric tube is substantially concentric. If a stent is patterned froma polymeric tube, a more concentric tube can result in more uniformthickness of struts, crowns and links of the stent. In some embodiments,the polymeric tube has a concentricity of about 0.0025 inch (about 64microns) or less, or about 0.002 inch (about 51 microns) or less, orabout 0.0015 inch (about 38 microns) or less, or about 0.001 inch (about25 microns) or less, or about 0.0005 inch (about 13 microns) or less. Infurther embodiments, the polymeric tube has a percent concentricity ofat least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,98% or 99%. In certain embodiments, the polymeric tube has aconcentricity of about 0.001 inch (about 25 microns) or less, or apercent concentricity of at least about 90%.

A substantially concentric polymeric tube can be made by, e.g., slowlyforming a tube thickness by spraying a solution or mixture of relativelylow polymer concentration onto a mandrel that is constantly rotating(clockwise and counter-clockwise) and moving axially (back and forthover the length of the mandrel).

In some embodiments, the first solution or mixture containing the firstbiodegradable polymer contains an additional biodegradable polymer or anon-degradable polymer, or both. The additional biodegradable polymercan be any biodegradable polymer described herein, and thenon-degradable polymer can be any non-degradable polymer describedherein. In some embodiments, the first solution or mixture containspoly(L-lactide) or a poly(L-lactide) copolymer, and an additionalbiodegradable polymer or a non-degradable polymer or both. In certainembodiments, the first solution or mixture contains poly(L-lactide) andpoly(ε-caprolactone).

The first biodegradable polymer, and any optional additionalbiodegradable polymer and/or any optional non-degradable polymer, can betreated prior to preparation of the first solution or mixture to removesubstantially residual water, solvent(s), monomer(s), low molecularweight oligomer(s) and/or particulate(s) from the polymer(s). In furtherembodiments, the first biodegradable polymer, and any optionaladditional biodegradable polymer and/or any optional non-degradablepolymer, are exposed to an extracting solvent (e.g., an alcohol, such asmethanol or ethanol), or to carbon dioxide gas or liquid under elevatedpressure (e.g., at least about 500, 600, 700, 800, 900 or 1000 psi forcarbon dioxide gas, or at least about 500, 1000, 2000, 3000, 4000 or5000 psi for carbon dioxide liquid) and optionally under a flow ofcarbon dioxide, e.g., at least about 10, 20, 30, 40 or 50 ccm (cubiccentimeter per minute), optionally at reduced or elevated temperature,for a period of time (e.g., at least about 1, 6, 12, 24, 36 or 48 hours)prior to preparation of the first solution or mixture containing thepolymer(s).

In additional embodiments, the first solution or mixture containing thefirst biodegradable polymer contains one or more biologically activeagents, or one or more additives, or both. The biologically activeagent(s) can be any biologically active agent described herein, and theadditive(s) can be any additive described herein. In certainembodiments, the biologically active agent(s) include myolimus ornovolimus.

Applying a mixture containing two or more substances or materials havingsignificantly different surface tensions can result in phase separationof the substances or materials. The following provides embodiments ofways for minimizing or preventing phase separation of substances ormaterials. Substances or materials having a substantially similarsurface tension are applied. If the substances or materials havesignificantly different surface tensions, a surfactant can be added tothe mixture. Exposure of the polymeric article to heat (in terms of,e.g., temperature and exposure time) is minimized during processing andduring any sterilization or storage of the article, and exposure of thedevice formed from the polymeric article to heat is minimized duringprocessing, sterilization and storage (e.g., the device is frozen duringsterilization with radiation and during storage).

In some embodiments, the method of making the device comprises:

(i) spraying the first solution or mixture containing the firstbiodegradable polymer and the first solvent onto the structure to form afirst layer containing the first biodegradable polymer, and

spraying a second solution or mixture containing a second biodegradablepolymer and a second solvent over at least a portion of the first layercontaining the first biodegradable polymer to form a second layer of thepolymeric article which contains the second biodegradable polymer; or

(ii) spraying a second solution or mixture containing a secondbiodegradable polymer and a second solvent onto the structure to form afirst layer containing the second biodegradable polymer, and

spraying the first solution or mixture containing the firstbiodegradable polymer and the first solvent over at least a portion ofthe first layer containing the second biodegradable polymer to form asecond layer of the polymeric article which contains the firstbiodegradable polymer.

The second biodegradable polymer can be any biodegradable polymerdescribed herein. In certain embodiments, the second solution or mixturecontaining the second biodegradable polymer contains an additionalbiodegradable polymer or a non-degradable polymer, or both. Theadditional biodegradable polymer can be any biodegradable polymerdescribed herein, and the non-degradable polymer can be anynon-degradable polymer described herein. Prior to preparation of thesecond solution or mixture, the second biodegradable polymer, and anyoptional additional biodegradable polymer and/or any optionalnon-degradable polymer, can be treated as described herein, e.g., toremove residual water, solvent(s), monomer(s), low molecular weightoligomer(s) and/or particulate(s) from the polymer(s). In certainembodiments, the second solution or mixture containing the secondbiodegradable polymer contains one or more biologically active agents,or one or more additives, or both. The biologically active agent(s) canbe any biologically active agent described herein, and the additive(s)can be any additive described herein.

The method of making the device can also comprise spraying a thirdsolution or mixture containing a third biodegradable polymer and a thirdsolvent, a fourth solution or mixture containing a fourth biodegradablepolymer and a fourth solvent, a fifth solution or mixture containing afifth biodegradable polymer and a fifth solvent, or additional polymersolution or mixture to form a third layer containing the thirdbiodegradable polymer, a fourth layer containing the fourthbiodegradable polymer, a fifth layer containing the fifth biodegradablepolymer, or additional polymer layer of the polymeric article, where thefirst layer, the second layer, the third layer, the fourth layer, thefifth layer, or additional layer can be in any order. The optional thirdbiodegradable polymer, the optional fourth biodegradable polymer and theoptional fifth biodegradable polymer can independently be anybiodegradable polymer described herein.

The optional third solution or mixture containing the thirdbiodegradable polymer, the optional fourth solution or mixturecontaining the fourth biodegradable polymer, and the optional fifthsolution or mixture containing the fifth biodegradable polymer can eachoptionally and independently contain an additional biodegradable polymeror a non-degradable polymer, or both. The additional biodegradablepolymer and/or the non-degradable polymer optionally in the thirdsolution or mixture, the fourth solution or mixture, and/or the fifthsolution or mixture can independently be any biodegradable polymerdescribed herein and any non-degradable polymer described herein. Priorto preparation of the optional third solution or mixture, the optionalfourth solution or mixture, and/or the optional fifth solution ormixture, the third biodegradable polymer, the fourth biodegradablepolymer, and/or the fifth biodegradable polymer, and any optionaladditional biodegradable polymer and/or any optional non-degradablepolymer, can be treated as described herein, e.g., to remove residualwater, solvent(s), monomer(s), low molecular weight oligomer(s) and/orparticulate(s) from the polymer(s). The optional third solution ormixture containing the third biodegradable polymer, the optional fourthsolution or mixture containing the fourth biodegradable polymer, and theoptional fifth solution or mixture containing the fifth biodegradablepolymer can each optionally and independently contain one or morebiologically active agents, or one or more additives, or both. Thebiologically active agent(s) and/or the additive(s) optionally in thethird solution or mixture, the fourth solution or mixture, and/or thefifth solution or mixture can independently be any biologically activeagent described herein and any additive described herein.

In some embodiments, the method of making the device comprisescrosslinking the first biodegradable polymer, the optional secondbiodegradable polymer, the optional third biodegradable polymer, theoptional fourth biodegradable polymer, or the optional fifthbiodegradable polymer, or any optional additional biodegradable polymeror any optional non-degradable polymer in the first layer, the optionalsecond layer, the optional third layer, the optional fourth layer, orthe optional fifth layer of the polymeric article, or crosslinking anycombination of the aforementioned polymers. In certain embodiments, thepolymer(s) are crosslinked by exposure to radiation (e.g., ultraviolet,e-beam or gamma radiation), exposure to heat, use of a degradable ornon-degradable crosslinker, or use of a crosslinking agent and aninitiator, as described herein.

The method of making the device can also comprise forming one or morelayers comprising a corrodible metal or metal alloy, and optionally anon-corrodible metal or metal alloy, to form the polymeric article. Thepolymeric article can comprise one or more polymer layers and one ormore metal layers in any order. For example, a metal layer, or each ofmultiple metal layers, or multiple metal layers, can lie between polymerlayers of the polymeric article. Further, the one or more metal layerscan be applied as a first outer layer, and/or as a second outer layer,of the polymeric article. For example, when the device is a stent, theone or more metal layers can be applied as a first outer layer, and/oras a second outer layer, of the polymeric tube which correspond to theluminal surface and the abluminal surface of the stent.

A metal layer can be applied using any suitable method, e.g., byapplying a metal film, foil or tube onto the structure (e.g., astructure having a flat surface and/or a contour surface) or over apolymer layer. If the implantable device is a stent, a stent can bepatterned from the polymeric article comprising one or more polymerlayers and one or more metal layers using any suitable method (e.g.,laser or mechanical cutting). Alternatively, a metal film, foil or tubehaving the desired stent pattern can be applied onto a mandrel or over apolymer layer (e.g., a metal tube having the desired stent pattern and aslightly larger diameter than the polymeric article can be crimped ontothe polymeric article). To enhance adhesion of a metal layer to apolymer layer and/or prevent separation or delamination thereof, themetal layer can be textured or treated, before and/or after beingapplied onto the structure or over a polymer layer, to form surfaceroughness, surface irregularities or surface features on one or moresurfaces of the metal layer. Surface roughness, surface irregularitiesand surface features of the metal layer can include, but are not limitedto, protrusions, spikes, pillars, ridges, mounds, bumps, textures,scratches, scores, streaks, dents, indentations, recesses, trenches,pores, pits, holes and cavities. Surface roughness, surfaceirregularities or surface features can be formed on the metal layer,before and/or after the metal layer is applied, by any suitable method,such as microblasting, beadblasting, sandblasting, treatment with acorrosive agent, treatment with an acid or base, treatment with water,chemical etching, physical or mechanical etching, or laser treatment, ora combination thereof.

The specific corrodible metal or metal alloy in a metal layer and thethickness of the metal layer can be selected to control characteristicsof the device, e.g., strength and degradation. If a non-corrodible metalor metal alloy is used in a metal layer, the specific non-corrodiblemetal or metal alloy and the amount thereof can be selected to impartdesired characteristics (e.g., enhanced strength and/or radiopacity)without unduly prolonging the degradation time of the device. In someembodiments, the thickness (e.g., average thickness) of a metal layer isabout 100 microns or less, or about 80 microns or less, or about 60microns or less, or about 50 microns or less, or about 40 microns orless, or about 30 microns or less, or about 20 microns or less, or about10 microns or less, or about 5 microns or less. In certain embodiments,the thickness (e.g., average thickness) of a metal layer is about 30microns or less, or about 20 microns or less.

As a non-limiting example of potential benefits of a metal layer, thepresence of one or more metal layers comprising a corrodible metal ormetal alloy, and optionally a non-corrodible metal or metal alloy, inthe body of a stent can enhance the strength of the stent and allow thestruts, crowns and/or links of the stent to have a smaller thicknessand/or a smaller width, thereby decreasing the amount of polymericmaterial used to make the body. In addition to increasing the strengthof the device, use of a non-corrodible metal or metal alloy in a metallayer, or as an additive, in the body of the device or in a coating onthe device can increase the radiopacity of the device, which maydispense with the use of a radiopaque marker.

Non-limiting examples of corrodible metals and metal alloys that canindependently comprise any metal layer(s) of the body of the deviceinclude cast ductile irons (e.g., 80-55-06 grade cast ductile iron),corrodible steels (e.g., AISI 1010 steel, AISI 1015 steel, AISI 1430steel, AISI 5140 steel and AISI 8620 steel), melt-fusible metal alloys,bismuth-tin alloys (e.g., 40% bismuth-60% tin and 58% bismuth-42% tin),bismuth-tin-indium alloys, magnesium alloys, tungsten alloys, zincalloys, shape-memory metal alloys, and superelastic metal alloys.Examples of non-corrodible metals and metal alloys that can optionallyand independently comprise any metal layer(s) include without limitationstainless steels (e.g., 316L stainless steel), cobalt-chromium alloys(e.g., L-605 and MP35N cobalt-chromium alloys), nickel-titanium alloys,gold, palladium, platinum, tantalum, and alloys thereof.

The polymeric article, whether associated with the structure or removedfrom the structure, can be treated to remove residual water, solvent(s),monomer(s), low molecular weight oligomer(s) and/or particulate(s) fromthe article. In some embodiments, the polymeric article is subjected toreduced pressure or heated at elevated temperature (e.g., at least about50, 60, 70, 80, 90 or 100° C.), or both, for a period of time (e.g., atleast about 0.5, 1, 6, 12, 24, 36 or 48 hours). In further embodiments,the polymeric article is exposed to an extracting solvent (e.g., analcohol, such as methanol or ethanol), or to carbon dioxide gas orliquid under elevated pressure (e.g., at least about 500, 600, 700, 800,900 or 1000 psi for carbon dioxide gas, or at least about 500, 1000,2000, 3000, 4000 or 5000 psi for carbon dioxide liquid) and optionallyunder a flow of carbon dioxide (e.g., at least about 10, 20, 30, 40 or50 ccm), optionally at reduced or elevated temperature, for a period oftime (e.g., at least about 0.5, 1, 6, 12, 24, 36 or 48 hours). Incertain embodiments, the material (e.g., polymeric material) comprisingthe polymeric article or the body of the device, or the material (e.g.,polymeric material) comprising each layer of the polymeric article orthe body of the device, comprises about 5, 4, 3, 2, 1.5, 1, 0.5 or 0.1wt % or less of each of water, solvent(s), monomer(s), low molecularweight oligomer(s) or particulate(s), or a combination thereof. In anembodiment, the material (e.g., polymeric material) comprising thepolymeric article or the body of the device, or the material (e.g.,polymeric material) comprising each layer of the polymeric article orthe body of the device, comprises about 2 wt % or less of each of water,solvent(s), monomer(s), low molecular weight oligomer(s) orparticulate(s), or a combination thereof.

The polymeric article, whether associated with the structure or removedfrom the structure, can also undergo any of a variety of treatmentsdesigned, e.g., to control crystallinity, enhance the strength ortoughness of the material (e.g., polymeric material) comprising thearticle, and/or reduce residual or internal stress in the polymericarticle. Control of crystallinity (e.g., degree of crystallinity) of thepolymeric material can achieve a suitable balance between the radialstrength (important for, e.g., support of the treated tubular tissue inthe subject) and the toughness (important for, e.g., resistance tocracking and fatigue) of the polymeric material. In certain embodiments,the polymeric article is removed from the structure prior to undergoinga modification or treatment. In some other embodiments, it is notremoved for at least one modification.

The polymeric article can also be deformed (e.g., contracted orexpanded) in any direction. Deforming the polymeric article in adirection can increase its strength along that direction (e.g., increaseits resistance to force applied in that direction). Furthermore,deforming the polymeric article in a direction can align polymer chainssubstantially in that direction and can induce crystallization andincrease crystallinity of the material (e.g., polymeric material)comprising the polymeric article, or can align amorphous polymer chainssubstantially in that direction without necessarily inducingcrystallization of the amorphous polymeric region or increasingcrystallinity of the material (e.g., polymeric material). In certainembodiments, the polymeric article is expanded in a direction (e.g.,longitudinal, circumferential or other direction) while being heated atelevated temperature (e.g., at or above the T_(g) of the polymericmaterial comprising the polymeric article), and then the expandedpolymeric article is cooled to a lower temperature (e.g., below T_(g)).

The polymeric article can be longitudinally extended by any suitablemethod. For example, if the polymeric article is a tube, a tubularstructure whose diameter is slightly less than the inner diameter of thepolymeric tube can be placed inside the tube, one end of the tube can beheld in place, and force can be applied to the other end of the tube tostretch the polymeric tube while maintaining the diameter of the tuberelatively uniform along the length of the tube. Moreover, the polymericarticle can be radially expanded by any suitable method. For example, ifthe polymeric article is a tube, an expandable pressure vessel can beplaced inside the tube and then gas or fluid, optionally heated, can beintroduced into the vessel to radially expand the polymeric tube to thedesired diameter. The expandable pressure vessel can optionally haveheating elements for heating the polymeric tube. An alternative methodof radial expansion of the polymeric tube is blow molding. The polymerictube can be placed inside a molding tube having an inner diameter equalto the desired expanded outer diameter of the polymeric tube.Pressurized inert gas (e.g., nitrogen or argon), optionally heated, canbe introduced into the molding tube to radially expand the polymerictube to the inner diameter of the molding tube. The molding tube canoptionally have heating elements for heating the polymeric tube.

In some embodiments, the polymeric article is longitudinally extendedand/or radially expanded, optionally while the polymeric article isheated at elevated temperature (e.g., at or above the T_(g) of thepolymeric material comprising the polymeric article) and optionally withcooling of the longitudinally extended and/or radially expandedpolymeric article to a lower temperature (e.g., below T_(g)), which canincrease the strength of the polymeric article and can induce orincrease orientation of crystals, crystalline regions or polymer chainssubstantially in the longitudinal direction, the circumferentialdirection, and/or a biaxial direction. In certain embodiments, thepolymeric article is radially expanded while being heated at elevatedtemperature (e.g., at or above the T_(g) of the polymeric materialcomprising the polymeric article) and then the radially expandedpolymeric article is cooled to a lower temperature (e.g., below T_(g)),which can increase the strength of the polymeric article and can induceor increase orientation of crystals, crystalline regions or polymerchains substantially in the circumferential direction or a biaxialdirection. In some embodiments, the polymeric article is longitudinallyextended by at least about 25%, 50%, 75%, 100%, 200%, 300%, 400% or 500%of its initial length, and/or radially expanded by at least about 25%,50%, 75%, 100%, 200%, 300%, 400% or 500% of its initial diameter. Incertain embodiments, the polymeric article is longitudinally extended byat least about 50% of its initial length, or radially expanded by atleast about 50% of its initial diameter, or both. In furtherembodiments, the polymeric article is longitudinally extended by atleast about 100% of its initial length, or radially expanded by at leastabout 100% of its initial diameter, or both.

Furthermore, the polymeric article can be rotated at a certain rate andfor a certain period of time, optionally with heating, to inducecircumferentially oriented stress, which can increase the radialstrength of the polymeric article and/or impart substantiallycircumferential or biaxial orientation to the polymeric materialcomprising the polymeric article. For example, a mandrel having apolymeric tube formed on it can be rotated at a certain rate and for acertain period of time, optionally with heating.

Another treatment that can, e.g., control crystallinity of the material(e.g., polymeric material) comprising the polymeric article is exposureof the polymeric article to radiation (e.g., ionizing radiation, such ase-beam radiation or gamma radiation). Ionizing radiation can be used tocontrol physical characteristics (e.g., control crystallinity or promotecrosslinking) of the material (e.g., polymeric material) comprising thepolymeric article without necessarily sterilizing the article, or tocontrol physical characteristics of the material and sterilize thepolymeric article. In some embodiments, the polymeric article is exposedto a single dose or multiple doses of e-beam or gamma radiation atambient temperature, or below or above ambient temperature, where a doseof radiation is at least about 0.1, 1, 5, 10, 20, 30, 40 or 50 kGray(kGy), or the total dose of radiation is about 1 or 5 kGy to about 100kGy, or about 5 or 10 kGy to about 60 kGy, or about 10 or 20 kGy toabout 50 kGy, or about 20 or 30 kGy to about 40 kGy. In certainembodiments, the polymeric article is cooled to reduced temperature(e.g., below 0° C.) and then is exposed to a single dose or multipledoses of e-beam or gamma radiation totaling about 10 kGy to about 50kGy.

The strength and/or toughness of the material(s) (e.g., polymericmaterial(s)] comprising the implantable device can also be enhanced byincorporation of one or more additives in the polymeric article fromwhich the device is formed, and/or by incorporation of one or moreadditives in a coating on the device. As an example, one or moreadditives (e.g., nanotubes, carbon nanotubes, fullerenes, nanoparticles,nanospheres, nanopowders, nanoclay, zeolites, exfoliates, fibers,whiskers, platelets, monomers, polymers, etc.) can be incorporated inthe polymeric article and/or a coating on the device to reinforce andstrengthen the material(s), e.g., polymeric material(s), comprising thepolymeric article and/or the coating. For example, fibers, particles orthe like comprised of the same polymer or a different biodegradable ornon-degradable polymer can be incorporated in the polymeric articleand/or a coating on the device to reinforce and strengthen thematerial(s), e.g., polymeric material(s), comprising the polymericarticle and/or the coating. In certain embodiments, the amount of eachof the one or more additives (e.g., nanotubes, carbon nanotubes,fullerenes, nanoparticles, nanospheres, nanopowders, nanoclay, zeolites,exfoliates, fibers, whiskers, platelets, monomers, polymers, etc.)incorporated in the polymeric article and/or a coating on the device isabout 0.1 or 0.5 wt % to about 10 wt %, or about 0.1 or 0.5 wt % toabout 5 wt %, or about 0.1, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6,7, 8, 9 or 10 wt %. As a further example, one or more additives, e.g.,solvents (e.g., dichloromethane and dimethylsulfoxide),glucosemonoesters, citrate esters, adipate esters, epoxidized soy oil,acetyl-tri-n-butyl citrate (ATBC), buturyl-tri-n-hexyl citrate (BTHC),di-iso-nonyl 1,2-cyclohexanedicarboxylate (DINCH), dioctyl terephthalate(DOTP), monomers (e.g., monomer(s) of the polymer(s) comprising thepolymeric article and/or the coating), and polymers (e.g., polyethylenecarbonate, polyethylene glycol, polyvinylpyrrolidone, andpolydimethylsiloxane), can be incorporated in the polymeric articleand/or a coating on the device to plasticize or soften the material(s),e.g., polymeric material(s) comprising the polymeric article and/or thecoating and make those material(s), e.g., polymeric material(s), moreductile and/or tougher.

If a solvent (e.g., dichloromethane or dimethylsulfoxide) is utilized asan additive, a controlled amount of the solvent (e.g., about 0.5 wt % toabout 5 wt %, or about 1 wt % to about 3 or 4 wt %, of the solventrelative to the weight of the material (e.g., polymeric material)comprising the body of the device or a coating on the device, orrelative to the weight of the device) can be incorporated in the body ofthe device and/or a coating on the device by, e.g., incorporating thesolvent in the polymeric article and/or a coating and controlling theparameters of any treatments (e.g., heating, vacuuming and/or exposureto carbon dioxide gas or liquid) that the polymeric article and/or thedevice undergo. In certain embodiments, about 1.5 or 2 wt % of a solvent(e.g., dichloromethane or dimethylsulfoxide) relative to the weight ofthe material (e.g., polymeric material) comprising the body of thedevice or a coating on the device, or relative to the weight of thedevice, is incorporated in the body of the device and/or a coating onthe device as an additive.

Depending on the type of device it is, the biodegradable implantabledevice may be able to be formed from the polymeric article when thepolymeric article is associated with the structure or removed from thestructure. For example, a stent can be patterned from a polymeric tube(e.g., by laser or mechanical cutting) when the tube is eitherassociated with a mandrel or removed from the mandrel. In certainembodiments, the polymeric article is removed from the structure priorto formation of the device from the polymeric article.

The implantable device can be formed from the polymeric article usingany suitable method or technique. In certain embodiments, the device isformed from the polymeric article by cutting the polymeric article witha laser to form a pattern of the device. The heat-affect zone andrecasting of the material (e.g., polymeric material) comprising thepolymeric article can be minimized by employing a laser having a shortpulse duration (e.g., a pulse duration in the nanoseconds orfemtoseconds). Non-limiting examples of lasers that can be used to cutthe polymeric article include excimer lasers and diode-pumpedsolid-state lasers operating at a wavelength of about 157 nm to about351 nm, or at about 193 nm, and femtosecond lasers and ultrafast lasersoperating at a wavelength of about 600 nm to about 1000 nm, or at about800 nm.

The implantable device can be any device described herein. When thedevice is a stent, the stent can be any stent described herein, and canhave any pattern and design suitable for its intended use, including anystent pattern and design described herein.

When the device is a stent, in some embodiments the stent is patternedfrom a polymeric tube that has a (e.g., inner) diameter substantiallyequal to an intended deployment (e.g., inner) diameter or the maximumallowable expansion (e.g., inner) diameter of the stent. In otherembodiments, the stent is patterned from a polymeric tube that has a(e.g., inner) diameter greater than (e.g., at least about 5%, 10%, 15%,20%, 25%, 30%, 35%, 40%, 45% or 50% greater than) an intended deployment(nominal or labeled) (e.g., inner) diameter or the maximum allowableexpansion (e.g., inner) diameter of the stent. In an embodiment, thestent is patterned from a polymeric tube that has a (e.g., inner)diameter at least about 10% greater than an intended (labeled ornominal) deployment (e.g., inner) diameter or the maximum allowableexpansion (e.g., inner) diameter of the stent. In some embodiments, thestent is patterned from a polymeric tube that has a (e.g., inner)diameter of about 2 mm to about 9 mm, or about 2 mm to about 7 mm, orabout 2 mm to about 5 mm, or about 2.5 mm to about 4.5 mm, or about 2.75mm to about 4.5 mm, or about 3 mm to about 4.5 mm, or about 2.75 mm toabout 4 mm, or about 3 mm to about 4 mm, or about 3.3 mm to about 3.8mm. In certain embodiments, the stent is patterned from a polymeric tubethat has a (e.g., inner) diameter of about 2.75 mm to about 4.5 mm, orabout 2.75 mm to about 4 mm. In some embodiments, prior to patterningthe stent from a polymeric tube, the diameter (e.g., inner diameter) ofthe polymeric tube is set by heating the tube at a temperature withinabout 10° C. or 5° C. of the T_(g), or at or above the T_(g), of thematerial (e.g., polymeric material) comprising the tube, and optionallycooling the tube to a temperature below the T_(g) (e.g., at least about5, 10, 15 or 20° C. below the T_(g), or to ambient temperature orbelow).

In some embodiments, the method of making the biodegradable implantabledevice comprises applying a first coating solution or mixture containinga biodegradable polymer or a non-degradable polymer, or both, and asolvent to the device to form a first coating disposed over or adjacentto at least a portion of the device. The biodegradable polymer of thefirst coating can be any biodegradable polymer described herein, and thenon-degradable polymer of the first coating can be any non-degradablepolymer described herein. In some embodiments, the biodegradable polymerof the first coating is a polylactide homopolymer or copolymer, whereinlactide includes L-lactide, D-lactide and D,L-lactide. In certainembodiments, the biodegradable polymer of the first coating is apoly(L-lactide) homopolymer or copolymer. In further embodiments, thebiodegradable polymer of the first coating is a copolymer of L-lactideand glycolide in a weight or molar ratio of about 70:30 to about99.9:0.1, or about 75:25 to about 95:5, or about 80:20 to about 90:10,or about 82:18 to about 88:12. In an embodiment, the biodegradablepolymer of the first coating is a copolymer of L-lactide and glycolidein a weight or molar ratio of about 85:15.

The solvent of the first coating solution or mixture can be any suitablesolvent for applying a polymer as described herein. In an embodiment,the solvent is dichloromethane. In some embodiments, the concentrationof the biodegradable polymer or the non-degradable polymer, or bothindividually or combined, in the first coating solution or mixture isabout 0.1 mg/mL to about 15 mg/mL, or about 0.5 mg/mL to about 10 mg/mL,or about 0.5 mg/mL to about 5 mg/mL, or about 1 mg/mL to about 3 mg/mL.In certain embodiments, the concentration of the biodegradable polymeror the non-degradable polymer, or both individually or combined, in thefirst coating solution or mixture is about 1 mg/mL to about 3 mg/mL, orabout 2 mg/mL.

In further embodiments, the first coating solution or mixture containsone or more biologically active agents, or one or more additives, orboth. The biologically active agent(s) of the first coating can be anybiologically active agent described herein, and the additive(s) of thefirst coating can be any additive described herein. In an embodiment,the biologically active agent(s) of the first coating include myolimusor novolimus. In some embodiments, the weight percentage of thebiologically active agent(s), individually or combined, relative to theamount of the biologically active agent(s) and the polymer(s) in thefirst coating solution or mixture is about 10% to about 60%, or about20% to about 60%, or about 30% to about 60%, or about 30% to about 50%,or about 40% to about 50%. In certain embodiments, the weight percentageof the biologically active agent(s), individually or combined, relativeto the amount of the biologically active agent(s) and the polymer(s) inthe first coating solution or mixture is about 30% to about 50%, orabout 40%.

In additional embodiments, the method of making the device comprisesapplying a second coating solution or mixture containing a biodegradablepolymer or a non-degradable polymer, or both, and a solvent to thedevice to form a second coating disposed over or adjacent to at least aportion of the first coating. The second coating solution or mixture cancontain one or more biologically active agents, or one or moreadditives, or both. The method can also comprise applying one or moreadditional coatings to the device. The biodegradable polymer, thenon-degradable polymer, the biologically active agent(s) and theadditive(s) of the second coating and any additional coating(s) canindependently be any biodegradable polymer described herein, anynon-degradable polymer described herein, any biologically active agentdescribed herein, and any additive described herein.

The first coating and any additional coating(s) can be applied to theimplantable device using any suitable method, e.g., by spraying therespective coating solution or mixture onto the device or dipping thedevice in the respective coating solution or mixture.

The coated device can be treated to incorporate or remove any residualwater, solvent(s), monomer(s), low molecular weight oligomer(s) and/orparticulate(s) from the coating(s) or the device. In some embodiments,the coated device is subjected to reduced or elevated pressure or heatedat elevated temperature (e.g., at least about 50, 60, 70, 80, 90 or 100°C.), or both, for a period of time (e.g., at least about 0.5, 1, 6, 12,24, 36 or 48 hours).

The coated device can also be treated to stabilize the coating(s) andprevent their smearing (e.g., upon expansion of the device). In someembodiments, the coated device is heated at about 50° C., 60° C., 70°C., 80° C., 90° C. or 100° C. or above, at ambient pressure or underreduced pressure, for a period of time (e.g., at least about 10 min, 30min, 1 hr, 4 hr, 8 hr or 12 hr). In certain embodiments, the coateddevice is heated at about 60° C. or above, at ambient pressure or underreduced pressure, for at least about 10 min To minimize degradation ofany biologically active agent(s) present in a coating or in the body ofthe device, the coated device can be heated in an inert environment(e.g., under nitrogen, argon or other inert gas).

In some embodiments, after the coated device undergoes any vacuum and/orheat treatments, the thickness (e.g., average thickness) of each of thefirst coating and any additional coating(s) independently is about 20microns or less, or about 15 microns or less, or about 10 microns orless, or about 5 microns or less, or about 4 microns or less, or about 3microns or less, or about 2 microns or less, or about 1 micron or less.In certain embodiments, after the coated device undergoes any vacuumand/or heat treatments, the thickness (e.g., average thickness) of eachof the first coating and any additional coating(s) independently isabout 10 microns or less, or about 5 microns or less. In furtherembodiments, after the coated device undergoes any vacuum and/or heattreatments, the thickness (e.g., average thickness) of the first coatingis about 5 microns or less, or about 3 microns or less.

As described herein, the body of the implantable device can comprisefeatures in and/or on the body, and/or a coating on the device cancomprise features in and/or on the coating, that promote degradation ofthe body and/or the coating. Examples of degradation-promoting featuresinclude without limitation openings, pores (including partial pores andthrough pores), holes (including partial holes and through holes),recesses, pits, cavities, trenches, reservoirs and channels.

Such degradation-promoting features can be formed by any of a variety ofways. For example, incorporation of an additive in the polymeric articleand/or a coating on the device and subsequent removal of the additive byexposure of the polymeric article and/or the device to a solvent thatdissolves the additive but does not substantially dissolve thepolymer(s) comprising the polymeric article and/or the coating can formpores in and/or on the body and/or the coating of the device. As anotherexample, incorporation of an additive (e.g., a blowing agent, a gas, asolvent or water) in the polymeric article and/or a coating on thedevice and subsequent removal of the additive by exposure of thepolymeric article and/or the device to heat and/or reduced pressure canform pores in and/or on the body and/or the coating of the device. Asstill another example, incorporation of an additive (e.g., a substancehaving a relatively low molecular weight of about 2,000 daltons or less)in the polymeric article and/or a coating on the device and subsequentremoval of the additive by exposure of the polymeric article and/or thedevice to carbon dioxide gas or liquid under elevated pressure,optionally under a flow of carbon dioxide, can form pores in and/or onthe body and/or the coating of the device. As yet another example, anadditive (e.g., a blowing agent) incorporated in the polymeric articleand/or a coating on the device can leach out from the polymeric article,the body of the device and/or the coating before and/or after the deviceis implanted in a subject to form pores in and/or on the body and/or thecoating of the device. As a further example, a certain amount of anadditive (e.g., about 4-10 wt %, or about 5 wt %, of carbon nanotubes)can be incorporated in the polymeric article and/or a coating on thedevice to form pores in and/or on the body and/or the coating of thedevice.

After a device is formed from the polymeric article, the device canundergo any of a variety of treatments designed, e.g., to control orreduce residual or internal stress in the device and/or to controlcrystallinity and/or control or enhance the strength or toughness of thematerial(s), e.g., polymeric material(s), comprising the body of thedevice and/or a coating on the device. In some embodiments, the deviceundergoes one or more cycles of heating and cooling to anneal thematerial(s), e.g., polymeric material(s). In certain embodiments, thedevice is heated at a temperature equal to or greater than the T_(g) ofthe first biodegradable polymer or the material (e.g., polymericmaterial) comprising the body of the device for a period of time (e.g.,at least about 0.1, 0.25, 0.5, 1, 4, 8, 12 or 24 hours), and thenquickly or slowly cooled to a lower temperature (e.g., at least about10° C., 20° C., 30° C., 40° C. or 50° C. below the T_(g), or to ambienttemperature or below) over a period of time (e.g., about 10 sec, 30 sec,1 min, 10 min, 30 min, 1 hr, 4 hr, 8 hr or 12 hr). In furtherembodiments, the device is heated at a temperature above the T_(g) andbelow the T_(m) of the first biodegradable polymer or the material(e.g., polymeric material) comprising the body of the device for aperiod of time (e.g., at least about 0.1, 0.25, 0.5, 1, 4, 8, 12 or 24hours), and then quickly or slowly cooled to a lower temperature (e.g.,at least about 10° C., 20° C., 30° C., 40° C. or 50° C. below the T_(g),or to ambient temperature or below) over a period of time (e.g., about10 sec, 30 sec, 1 min, 10 min, 30 min, 1 hr, 4 hr, 8 hr or 12 hr). Incertain embodiments, the device is heated at a temperature within thecold crystallization temperature range of the first biodegradablepolymer or the material (e.g., polymeric material) comprising the bodyof the device for a period of time (e.g., at least about 0.1, 0.25, 0.5,1, 4, 8, 12 or 24 hours), and then quickly or slowly cooled to a lowertemperature (e.g., at least about 10° C., 20° C., 30° C., 40° C. or 50°C. below the T_(g), or to ambient temperature or below) over a period oftime (e.g., about 10 sec, 30 sec, 1 min, 10 min, 30 min, 1 hr, 4 hr, 8hr or 12 hr). In still further embodiments, the device is heated at atemperature equal to or greater than the T_(m) of the firstbiodegradable polymer or the material (e.g., polymeric material)comprising the body of the device for a period of time (e.g., at leastabout 0.1, 0.25, 0.5, 1, 4, 8, 12 or 24 hours) to melt crystallineregions of the first biodegradable polymer or the material (e.g.,polymeric material), and then quickly or slowly cooled to a lowertemperature (e.g., at least about 10° C., 20° C., 30° C., 40° C. or 50°C. below the T_(g), or to ambient temperature or below) over a period oftime (e.g., about 10 sec, 30 sec, 1 min, 10 min, 30 min, 1 hr, 4 hr, 8hr or 12 hr).

Another treatment that can, e.g., control crystallinity of thematerial(s), e.g., polymeric material(s) comprising the body of thedevice and/or a coating on the device is exposure of the device toradiation (e.g., ionizing radiation, such as e-beam radiation or gammaradiation). Ionizing radiation can be used to control physicalcharacteristics (e.g., control crystallinity or promote crosslinking) ofthe material(s), e.g., polymeric material(s), comprising the body of thedevice and/or a coating on the device without necessarily sterilizingthe device, or to control physical characteristics of the material(s)and sterilize the device. In some embodiments, the device is exposed toa single dose or multiple doses of e-beam or gamma radiation at ambienttemperature, or below or above ambient temperature, where a dose ofradiation is at least about 0.1, 1, 5, 10, 20, 30, 40 or 50 kGy, or thetotal dose of radiation is about 1 or 5 kGy to about 100 kGy, or about 5or 10 kGy to about 60 kGy, or about 10 or 20 kGy to about 50 kGy, orabout 20 or 30 kGy to about 40 kGy. In certain embodiments, the deviceis cooled to reduced temperature (e.g., below 0° C.) and then is exposedto a single dose or multiple doses of e-beam or gamma radiation totalingabout 10 kGy to about 50 kGy, or about 30 kGy.

Furthermore, the device can be rotated at a certain rate and for acertain period of time, optionally with heating, to inducecircumferentially oriented stress, which can increase the radialstrength of the device and/or impart substantially circumferential orbiaxial orientation to the polymeric material comprising the body of thedevice. For example, a mandrel having a stent associated with it can berotated at a certain rate and for a certain period of time, optionallywith heating.

When the implantable device is a stent, the stent can be crimped to areduced diameter so that the stent can be delivered through a vessel orpassage of a subject. In some embodiments, the stent is crimped to aninner diameter of about 0.4 mm, 1 mm to about 2 mm, or about 1.2 mm toabout 1.6 mm, or about 1.3 mm to about 1.5 mm. In certain embodiments,the stent is crimped to an inner diameter of about 1.3 mm to about 1.5mm, or about 1.4 mm.

In some embodiments, the stent is crimped at ambient temperature, or iscrimped at a temperature (crimping temperature) of at least about 30°C., 35° C., 40° C., 45° C. or 50° C., and the stent crimped at elevatedtemperature is then cooled to a lower temperature (e.g., at least about5° C., 10° C., 15° C., 20° C., 25° C. or 30° C. below the crimpingtemperature, or to ambient temperature or below). In certainembodiments, the stent is crimped at about 40° C. or above, and thecrimped stent is then cooled to a temperature at least about 5° C. belowthe crimping temperature. Radially inward recoil of the stent after itis deployed can be reduced by crimping the stent at a temperature atabout the T_(g) or below the T_(g) of the material (e.g., polymericmaterial) comprising the stent body. In certain embodiments, the stentis crimped at an elevated temperature that is at about the T_(g) or atleast about 1° C., 5° C., 10° C., 15° C., 20° C., 25° C., 30° C., 35°C., 40° C., 45° C. or 50° C. below the T_(g) of the material (e.g.,polymeric material) comprising the stent body. In an embodiment, thestent is crimped at an elevated temperature that is at least about 5° C.below the T_(g) of the material (e.g., polymeric material) comprisingthe stent body.

Furthermore, the conditions in which the crimped stent is treated andhandled can affect cracking, recoil, radial strength and uniformity ofradial expansion of the stent. Minimizing exposure of the crimped stentto heat (in terms of, e.g., temperature and exposure time) can decreasecracking and recoil and improve radial strength and uniformity of radialexpansion. Heat may promote generation of a crimped-state memory and maypromote erasure of some amount of the as-cut tube memory (the diameterof the tube used to pattern the stent). For example, cracking and recoilcan be decreased and radial strength and uniformity of radial expansioncan be improved by exposing the crimped stent to a temperature notexceeding the T_(g), or at least about 1° C., 5° C., 10° C., 15° C., 20°C., 25° C. or 30° C. below the T_(g), of the material (e.g., polymericmaterial) comprising the stent body during, e.g., stabilization of thestent in the crimped state, mounting of the crimped stent onto aballoon-catheter, sterilization of the stent delivery system (e.g., withe-beam), and storage.

During storage of a crimped stent, the presence of heat (whether addedor not) may induce crystallization of the polymeric material comprisingthe stent body over time. Crystallization of the polymeric material mayor may not be accompanied by increase in the glass transitiontemperature of the polymeric material, and may render the polymericmaterial more brittle. Greater brittleness of the polymeric material mayincrease cracking of crowns of the stent upon radial expansion of thestent. Crystallization of the polymeric material during storage may alsostrengthen the crimped-state memory and may weaken the as-cut tubememory of the stent, which may result in less uniform radial expansionof the stent and greater radially inward recoil of the stent afterexpansion.

Crystallization of the polymeric material comprising the body of thecrimped stent during storage can be reduced by any of a variety of ways.As a non-limiting example, the stent body can be comprised of apolymeric material that does not crystallize or increase incrystallinity over time and/or in the presence of heat (whether added ornot). For example, the stent polymeric material can already be at itsmaximum % crystallinity prior to storage of the crimped stent, providedthat the polymeric material is not too brittle and is sufficientlytough. As another example, one or more crystallization-inhibitingadditives can be incorporated in the material (e.g., polymeric material)comprising the stent body. In certain embodiments, thecrystallization-inhibiting additive(s) leach out from the stent materialafter exposure of the stent to physiological conditions. As yet anotherexample, the crimped stent (or stent delivery system) can be stored atreduced temperature (e.g., at about 10° C., 5° C., 0° C., −5° C., −10°C. or −20° C. or below). Or the stent can be formed from a polymerictube comprised of a polymeric material that has a low % crystallinity,so that any increase in crystallinity of the polymeric material duringstorage of the crimped stent does not result in a final % crystallinitythat may adversely affect physical properties of the stent.

In some embodiments, prior to sterilization the crimped stent isstabilized in the crimped state at about 20° C. to about 35° C., or atabout 25° C. to about 30° C., or at about 30° C., or at about 30° C. toabout 35° C., or at about 35° C. to about 45° C.; for at least about 0.1hr, 1 hr, 2 hr, 3 hr, 4 hr, 8 hr, 12 hr, 16 hr or 24 hr, or longer. Thecrimped stent can be mounted onto a balloon-catheter to provide a stentdelivery system. In certain embodiments, after sterilization (e.g., withe-beam) the crimped stent, or the stent mounted on a balloon-catheter,is stabilized in the crimped state at about 20° C. to about the T_(g) ofthe material (e.g., polymeric material) comprising the body of thestent, or at about 5° C., 10° C., 15° C., 20° C., 25° C. or 30° C. belowthe T_(g), or at about 20° C. to about 30° C., or at about 25° C., or atabout 30° C. to about 35° C., or at about 35° C. to about 45° C.; for atleast about 0.1 hr, 1 hr, 4 hr, 6 hr, 12 hr, 24 hr, 36 hr, 48 hr, 60 hr,72 hr, 84 hr or 96 hr, or longer. Stabilization of the mounted stent inthe crimped state can enhance or control its retention on the balloon ordelivery system during delivery through a vessel or a passage in asubject or upon expansion inside a blood vessel.

Retention of a stent on a balloon-catheter can also be enhanced byforming the inner (luminal) layer of the stent body from, or coating theluminal surface of the stent with, an elastomeric polymeric material,e.g., poly(ε-caprolactone), with a relatively high coefficient offriction. The relatively high-friction polymeric material can minimizemovement of the stent on the balloon.

Additional ways for improving retention of a stent on a balloon-catheterinclude use of a non-permanent adhesive applied to the balloon or theluminal surface of the stent, or both. In some embodiments, the adhesiveis made from a hydrophobic material that can resist water and lose itstackiness when exposed to water. In certain embodiments, the adhesivehas weak bond force in the shear direction.

Raised portions (poofs) formed on the balloon of a balloon-catheter andlocated at the proximal and distal ends of a stent can maintain thestent on the balloon. Poofs located above the balloon markers of thecatheter can be formed on the balloon (see, e.g., Example 1). Forexample, the balloon poofs can be designed to cap the proximal anddistal ends of the stent (FIG. 2).

Furthermore, the abluminal surface, the luminal surface and both sidesurfaces of a crimped stent can be partially or fully covered by awater-soluble or non soluble material that dissolves away after acertain period of time. Coverage of the stent by the water-soluble ornon soluble material reduces permeation of water into the body of thestent, which prevents the stent from growing or swelling above theballoon poofs, thereby helping to retain the stent on the balloon.

Cap(s) can be placed on the proximal end and/or the distal end of acrimped stent to maintain the stent on a balloon-catheter. A majorportion of the cap can be on the balloon-catheter, and a minor portionof the cap can be extended over the stent. In certain embodiments, thecap covers at most one full crown of the stent, or at most half a crown.The cap can be fitted tightly against the balloon portion of thecatheter or be bonded to the catheter. Prior to radial expansion of thestent, the cap maintains the stent on the balloon-catheter. Duringradial expansion of the stent, the cap recesses, allowing the stent toexpand without hindrance. The cap can be solid and be substantially freeof holes, or can be a mesh or have holes.

Moreover, a stent can have locks or lockable elements that help toretain the stent on a balloon-catheter. FIG. 3 illustrates anon-limiting example of a stent pattern having lockable elements. Whenthe stent is crimped, the arrow or male on one side of a lockableelement engages with the other side or female of an adjacent lockableelement and locks in place. Locking of the lockable elements preventsthe stent from growing, thereby helping to retain the stent on theballoon.

A crimped stent can also be maintained on a balloon-catheter by placinga retractable sheath or sleeve over the stent. The sheath or sleeve canend at or beyond the proximal end and/or the distal end of the stent, orover the stent. The sheath or sleeve can be physically or mechanicallyretracted from the stent prior to radial expansion of the stent.

In addition, a stent can be retained on a balloon by placing or crimpinga protector stent over the main stent. In certain embodiments, theprotector stent is thin (e.g., about 0.001 inch thick) and has arelatively high degree of crystallinity or a relatively high T_(g). Theprotector stent may not grow when exposed to physiological conditions,may not expand evenly or may crack, but the main stent is the stent thatis designed to expand substantially evenly and support the treatedvessel.

In some embodiments, the biodegradable stent is retained on aballoon-catheter by any suitable means, including any means describedherein, and is configured not to move on the balloon-catheter in atleast one longitudinal direction by more than about 5 mm, 4 mm, 3 mm, 2mm, 1 mm or 0.5 mm, e.g., during delivery of the stent-catheter systemthrough a vessel or passage of a subject. In an embodiment, the stent isconfigured not to move on the balloon-catheter in at least onelongitudinal direction by more than about 1 mm.

The device (e.g., a crimped or uncrimped stent or a stent deliverysystem) can be subjected to a sterilization condition. Subjecting thedevice to a sterilization condition can serve purposes in addition tosterilization of the device, such as controlling crystallinity of thematerial(s), e.g., polymeric material(s), comprising the device.Non-limiting examples of sterilization conditions include radiation,ionizing radiation, e-beam radiation, gamma radiation, and ethyleneoxide gas. In some embodiments, the device is exposed to a single doseor multiple doses of e-beam or gamma radiation at ambient temperature,or below or above ambient temperature, where a dose of radiation is atleast about 0.1, 1, 5, 10, 20, 30, 40 or 50 kGray (kGy), or the totaldose of radiation is about 1 or 5 kGy to about 100 kGy, or about 5 or 10kGy to about 60 kGy, or about 10 or 20 kGy to about 50 kGy, or about 20or 30 kGy to about 40 kGy.

For sterilization the device (e.g., a crimped or uncrimped stent or astent delivery system) can also be exposed to ethylene oxide gas in asuitable environment (e.g., a sealed bag or a chamber). As anon-limiting example of sterilization with ethylene oxide gas, thedevice is preconditioned for about 1 hr at a relative humidity of atleast about 35% and at a temperature of about ambient temperature toabout 33° C. The device is exposed to ethylene oxide gas at atemperature of about ambient temperature to about 33° C., or at about25° C., or between about 20° C. to about 40° C.; for at least about 4hr, 8 hr, 12 hr, 16 hr, 24 hr or 30 hr. Sterilization can be conductedin the presence of water chips (e.g., two 4 g water chips) to increasehumidity. As another example of sterilization with ethylene oxide gas,the device is exposed to ethylene oxide gas at a temperature of about35° C. to about 50° C., or about 35° C. to about 45° C., and at arelative humidity of about 20% to about 80%, or about 30% to about 70%,for at least about 4 hr, 8 hr, 12 hr, 16 hr or 24 hr. To avoidgeneration of a crimped-state memory at higher temperature, a stent canbe mounted onto an inflated balloon prior to sterilization, sterilizedwith ethylene oxide gas at elevated temperature, and then crimped ontothe deflated balloon in an aseptic or semi-aseptic environment. Thestent-balloon-catheter delivery system can be terminally sterilized byexposure to nitrogen dioxide at about ambient temperature or below forat least about 10, 30, 60, 90 or 120 minutes, using, e.g., a systemdeveloped by Noxilizer (Baltimore, Md.).

In addition to spraying, the biodegradable implantable devices such asthe stent (scaffold) described herein can be made by other suitablemethods, such as dipping, extrusion, molding, injection molding,compression molding and 3-D printing. For example, a polymericarticle/material (e.g., a polymeric tube) can be made by dipping astructure (e.g., a substantially cylindrical structure) in a solution ormixture containing one or more biodegradable polymers and a solvent, andoptionally one or more non-degradable polymers, one or more biologicallyactive agents, and one or more additives. A device (e.g., a stent) canbe formed from the polymeric article (e.g., by laser or mechanicalcutting) while the article is associated with the structure or after thearticle is removed from the structure. A polymeric article made bydipping, and/or a device formed from such a polymeric article, canundergo any one or more of the processing steps and treatments describedherein (e.g., longitudinal extension, radial expansion, heating,pressurizing, vacuuming, or exposure to radiation or carbon dioxide, ora combination thereof).

Dipping can also be performed to make a polymeric article (e.g., apolymeric tube) comprising two or more polymer layers, where each layerindependently contains one or more biodegradable polymers, andoptionally one or more non-degradable polymers, one or more biologicallyactive agents, and one or more additives. After a structure (e.g., asubstantially cylindrical structure) is dipped in and then removed froma first solution or mixture containing one or more biodegradablepolymers and optional additional material(s) or substance(s), the coatedstructure is suitably dried by any of various treatments describedherein (e.g., vacuuming, heating, and/or exposure to carbon dioxide gasor liquid). The coated structure is dipped in and then removed from asecond solution or mixture containing one or more biodegradable polymersand optional additional material(s) or substance(s), and is suitablydried to form a second polymer layer of the polymeric article. Thedipping and drying process can be repeated a desired number of times toform a desired number of polymer layers of the polymeric article.

Moreover, a polymeric article (e.g., a polymeric tube) comprising one ormore polymer layers and one or more metal layers can be made by dipping.For example, a metal film, foil or tube comprising a corrodible metal ormetal alloy, and optionally a non-corrodible metal or metal alloy, canbe applied to a coated structure made by dipping the structure (e.g., asubstantially cylindrical structure) in a first solution or mixturecontaining one or more biodegradable polymers, and optionally one ormore non-degradable polymers, one or more biologically active agents,and one or more additives. The metal film, foil or tube can bepre-textured or pre-treated (e.g., by microblasting) prior to itsapplication to form surface roughness on one side of the metal film,foil or tube to enhance its adhesion to the first polymer layer. Asecond polymer layer can be applied to the metal layer, the other sideof the metal film, foil or tube can be pre-textured or pre-treated, orcan be treated after its application to the first polymer layer, to formsurface roughness on the uncoated side of the metal layer before thestructure is dipped in a second solution or mixture containing one ormore biodegradable polymers and optional additional material(s) orsubstance(s).

The following provides embodiments of ways for making a polymeric tubeby dipping. A mandrel, whose diameter can be substantially equal to orlarger than an intended deployment inner diameter of a stent to beformed from the tube, is dipped in a solution or mixture containing oneor more biodegradable polymers and a solvent, and optionally one or morenon-degradable polymers, one or more biologically active agents, and oneor more additives. The concentration of the material(s) in the solutionor mixture can be about 1 or 5 mg/mL to about 100 mg/mL, or about 10 or20 mg/mL to about 50 mg/mL. The mandrel can be dipped in the polymersolution or mixture with or without rotation of the mandrel. After themandrel is dipped in the polymer solution or mixture for a period oftime (e.g., at least about 1, 2, 3, 4, 5, 10 or 15 seconds), the mandrelis removed from the polymer solution or mixture at a certain rate thatmay depend on the desired thickness of the coating/layer or tube (if thetube contains only one polymer layer). More than one cycle of dippingand removal can be performed depending on, e.g., the concentration ofthe polymer solution or mixture and the desired thickness of thecoating/layer or tube. After removal of the mandrel from the polymersolution or mixture, the coated mandrel can be rotated (e.g., held androtated in a horizontal position) or not rotated. The coated mandrel canundergo vacuuming and/or heating to remove, e.g., any residualsolvent(s) and monomer(s). The coated mandrel can also be exposed tocarbon dioxide gas or liquid under elevated pressure to remove, e.g.,any residual solvent(s), monomer(s), low molecular weight oligomer(s)and/or particulate(s). The thickness and physical characteristics of thecoating/layer or tube can be controlled by controlling variousparameters, such as the composition and concentration of the polymersolution or mixture, the number of times the mandrel is dipped in thepolymer solution or mixture, the duration of each dip, the rate ofremoval of the mandrel from the polymer solution or mixture, and theconditions and duration of drying after each dip. If the polymeric tubeis to comprise a second polymer layer, the suitably dried coated mandrelis dipped in a second solution or mixture containing one or morebiodegradable polymers and a solvent, and optionally one or morenon-degradable polymers, one or more biologically active agents, and oneor more additives. A stent can be patterned from the polymeric tube by,e.g., laser or mechanical cutting while the tube remains on the mandrelor after the tube is removed from the mandrel.

Dipping can provide a polymeric tube comprised of a polymeric materialthat is, or has crystals, crystalline regions or polymer chains thatare, substantially randomly oriented or substantially not uniaxiallyoriented, circumferentially oriented, longitudinally oriented orbiaxially oriented, if desired. To promote formation of a polymeric tubecomprised of a polymeric material that is substantially not uniaxiallyoriented or biaxially oriented, certain parameters of the dippingprocess can be controlled, such as the concentration of the polymersolution or mixture, the rate and direction of dipping (e.g., the lengthof the mandrel is dipped in the polymer solution or mixturehorizontally, vertically or at an angle), the rate of rotation, if any,of the mandrel while dipped in the polymer solution or mixture, the rateof removal of the mandrel from the polymer solution or mixture, and therate of rotation, if any, of the coated mandrel after removal from thepolymer solution or mixture.

Extrusion is another non-limiting example of a method for makingbiodegradable implantable devices described herein. For example, one ormore biodegradable polymers, and optionally one or more non-degradablepolymers, one or more additives, and one or more biologically activeagents [if the heating is compatible with the bioactive agent(s)], canbe heated and drawn through a die to make a polymeric article (e.g., apolymeric tube). A device (e.g., a stent) can be formed from thepolymeric article using any suitable method (e.g., laser or mechanicalcutting). To make a polymeric tube comprising two or more polymerlayers, two or more tubings can be co-drawn, where each tubingindependently contains one or more biodegradable polymers, andoptionally one or more non-degradable polymers, one or more additives,and one or more biologically active agents.

Drawing the extruded material in a particular direction, optionally atelevated temperature, may induce or increase orientation of thematerial, or its crystals, crystalline regions or polymer chains,substantially in that direction. If desired, the following providesembodiments of ways for making a polymeric article (e.g., a polymerictube) by extrusion, where the article is comprised of a polymericmaterial that is, or has crystals, crystalline regions or polymer chainsthat are, substantially randomly oriented or substantially notuniaxially oriented, circumferentially oriented, longitudinally orientedor biaxially oriented. As a first embodiment, a polymeric material isextruded at elevated temperature in the presence of a crystallizationinhibitor that inhibits crystallization of the polymeric material whilethe material cools down after it exits the hot extruder nozzle.

As a second embodiment, a polymeric material is extruded at elevatedtemperature. Immediately after the polymeric material exits the hotextruder nozzle, the polymeric material is rapidly cooled below itscrystallization temperature (T_(c)) or glass transition temperature(T_(g)), or to ambient temperature or below, to prevent or minimizecrystallization of the polymeric material. The resulting polymericarticle (e.g., polymeric tube) can be formed into a device (e.g., astent).

As a third embodiment, a polymeric material is extruded at elevatedtemperature with a minimal drawing ratio. The resulting polymericarticle (e.g., polymeric tube) is heated to about or above the meltingtemperature (T_(m)) of the polymeric material comprising the article.The polymeric material is rapidly cooled below its T_(c) or T_(g), or toambient temperature or below, to prevent or minimize crystallization ofthe polymeric material. The resulting polymeric article can be formedinto a device (e.g., a stent).

One embodiment is a process for making a biodegradable polymeric stent(or other endoprosthesis having a tubular body) according to the presentteachings. A tubular body (e.g., a tube) comprised of a biodegradablepolymeric material (having a degree of crystallinity of about 30%, 20%,15%, 10% or 5% or less) is made by any suitable method, such asspraying, dipping, extrusion, molding, injection molding, compressionmolding or 3-D printing, e.g., by spraying onto a mandrel. The polymerictube undergoes one or more cycles of heating and cooling (or step-wiseheating and then cooling) as described herein, e.g., to increasecrystallinity and/or strength of the material (e.g., polymeric material)the tube, and/or to reduce residual or internal stress in the polymerictube. After the one or more cycles of heating and cooling or radiation,the degree of crystallinity of the material (e.g., polymeric material)is about 2%, 5% or 10% to about 70%, or about 2%, 5% or 10% to about60%, or about 2%, 5% or 10% to about 50%, or about 2%, 5% or 10% toabout 40%, or about 2%, 5% or 10% to about 30%, or about 2%, 5% or 10%to about 20%, or increases by at least about 10%, 20%, 25%, 30%, 40%,50%, 75%, 100%, 150%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900% or1000%. The heat-treated or radiated polymeric tube is patterned into astent or other endoprosthesis having a tubular body using any suitablemethod (e.g., laser or mechanical cutting). Alternatively, a stent orother endoprosthesis can be patterned from a polymeric tube that has notundergone a heat treatment, and the stent or other endoprosthesis canundergo one or more cycles of heating and cooling. As a furtheralternative, both the polymeric tube and the stent or otherendoprosthesis can each undergo one or more cycles of heating andcooling.

Residual or internal stress may arise during processing of a polymericarticle (e.g., a polymeric tube) or a device (e.g., a stent) formed fromthe polymeric article. Residual/internal stress may cause failure (e.g.,substantial shortening, shrinkage, warping or the like) of the device ifthe level of residual/internal stress is high enough to overcome thestructural integrity of the device. A polymeric article (e.g., apolymeric tube) made by extrusion or molding or spraying may requirestabilization (which can include heating and pre-shrinkage) to relieveresidual/internal stress and minimize shortening, shrinkage, warping orthe like. Preparation of a polymeric article (e.g., a polymeric tube) byspraying can decrease the level of residual/internal stress in thearticle without resorting to stabilization.

Further embodiments of the disclosure relate to a method of making abiodegradable endoprosthesis, comprising providing a polymeric article(e.g., a tubular body, such as a polymeric tube) composed at leastpartially of a substantially amorphous or semi-crystalline,biodegradable polymeric material, wherein crystallinity (e.g., degree ofcrystallinity) of the polymeric material increases after the polymericarticle undergoes a modification (or treatment), and wherein theendoprosthesis is formed from the polymeric article. The polymericmaterial is substantially amorphous or semi crystalline or crystallineprior to the modification, and may or may not be substantially amorphousafter the modification. Further embodiments of the disclosure relate toa method of making a biodegradable endoprosthesis, comprising providinga polymeric article (e.g., a tubular body, such as a polymeric tube)comprising at least partially of a substantially amorphous orsemi-crystalline biodegradable polymeric material, wherein crystallinity(e.g., degree of crystallinity) of the polymeric material decreasesafter the polymeric material undergoes a treatment, and wherein theendoprosthesis is formed substantially from the polymeric material. Inone embodiment, the polymeric material is substantially amorphous orsemi crystalline or crystalline prior to the modification, andsubstantially amorphous after the modification. In certain embodiments,the modification comprises heating, cooling, quenching, pressurizing,vacuuming, crosslinking, addition of an additive, or exposure toradiation or carbon dioxide, or a combination thereof. The polymericarticle can have any shape, form and dimensions suitable for making theendoprosthesis (e.g., a patterned polymeric tube stent).

In some embodiments, a biodegradable endoprosthesis (e.g., a stent) isformed from a polymeric tube, wherein the tube is a substantiallycontinuous cylinder that is substantially free from holes, gaps, voidsor other discontinuities. In some embodiments, the polymeric tube has anoutside diameter of about 2 mm to about 10 mm, or about 2 mm to about 5mm; a thickness of about 0.01 mm to about 0.5 mm, or about 0.05 mm toabout 0.3 mm; and a length of about 2 or 5 mm to about 20, 30, 40 or 80mm. In certain embodiments, the polymeric tube has an outside diameterof about 2 mm to about 5 mm, a thickness of about 0.05 mm to about 0.3mm, and a length of about 5 mm to about 30 mm.

In certain embodiments, an endoprosthesis (e.g., a stent) is patternedby laser cutting or other method from a polymeric tube that has a (e.g.,inner or outer) diameter substantially equal to or smaller than anintended deployed (e.g., inner or outer) diameter of the endoprosthesis.In other embodiments, an endoprosthesis (e.g., a stent) is patternedfrom a polymeric tube that has a (e.g., inner or outer) diameter, eitherwhen the tube is formed or after the tube is radially expanded to asecond larger diameter, larger than an intended deployed (e.g., inner orouter) diameter of the endoprosthesis. Patterning a stent from apolymeric tube having a (e.g., inner or outer) diameter larger than anintended deployed (e.g., inner or outer) diameter of the stent canimpart advantageous characteristics to the stent, such as reducingradially inward recoil of the stent after deployment. In certainembodiments, a stent is patterned from a polymeric tube having a (e.g.,inner or outer) diameter about 0.85, 0.90, 1.0, 1.05 to about 1.5 times,or about 1.1 to about 1.5 times, or about 1.1 to about 1.3 times, orabout 1.15 to about 1.25 times, smaller, same, or larger than anintended deployed (e.g., inner or outer) diameter of the stent. In anembodiment, the stent is patterned from a polymeric tube having a (e.g.,inner or outer) diameter about 1.1 to about 1.3 times larger than anintended deployed (e.g., inner) diameter of the stent. For example, astent having a deployed (e.g., inner or outer) diameter of about 2.5, 3or 3.5 mm can be patterned from a tube having a (e.g., inner or outer)diameter of about 2.75, 3.3 or 3.85 mm (1.1 times larger), or about3.25, 3.9 or 4.55 mm (1.3 times larger), or some other (e.g., inner orouter) diameter larger than the deployed (e.g., inner or outer) diameterof the stent. In other embodiments, the initial diameter of the formedtube is larger than the crimped diameter (e.g., crimped diameter on adelivery system) of the stent prosthesis wherein the tubular body isexpanded to a second larger diameter than the initial diameter beforepatterning or before crimping to the crimped diameter; or wherein thetubular body remains substantially the same diameter before patterningor before crimping to a crimped diameter; or wherein the tubular body iscrimped to a smaller diameter than the initial formed diameter beforepatterning or after patterning. In another embodiment, the initialdiameter of the formed tube is smaller than the crimped diameter of thestent prosthesis wherein the tubular body is expanded to a second largerdiameter than the initial diameter before patterning or before crimping;or wherein the tubular body remains substantially the same diameterbefore patterning or before crimping; or wherein the tubular body iscrimped to a smaller diameter than the crimped diameter of the stentprosthesis before patterning or after patterning. In another embodiment,the initial diameter of the formed tubular body is greater than 0.015inches, or greater than 0.050 inches, or greater than 0.092 inches, orgreater than 0.120 inches, or greater than 0.150 inches. Stentprosthesis intended deployment diameter is the diameter of the labeleddelivery system or balloon catheter. For example when a stent prosthesisis crimped onto a balloon labeled 3.0 mm diameter, the stent prosthesis'intended deployment diameter is 3.0 mm. Similarly, self expandable stentcrimped onto a delivery system is labeled a certain deployment diameter.

The stent cut from a polymeric tube can be any kind of stent and canhave any pattern and design suitable for its intended use, including anykind of stent and any pattern and design described herein. Further, thestent can be a fully self-expandable stent, a balloon-expandable stent,or a stent capable of radially self-expanding prior to balloon expansionto an intended deployed diameter.

The degree of crystallinity of the material (e.g., polymeric material)of which an endoprosthesis (e.g., a stent) is comprised may decline as aresult of cutting of the polymeric article (e.g., a polymeric tube). Insome embodiments, a stent is annealed and quenched one or more timesafter cutting of the polymeric tube, as described herein for annealingand quenching a polymeric article or tube, to increase the degree ofcrystallinity of the polymeric material (and/or reduce residual/internalstress in the polymeric material or the stent). In certain embodiments,a heat-treated stent is cooled to a temperature below ambienttemperature for a period of about 1 minute to about 96 hours, or about24 hours to about 72 hours, or about 30 minutes to about 48 hours, orabout 1 hour to about 48 hours, or about 1 hour to about 36 hours, orabout 1 hour to about 24 hours, or about 1 hour to about 12 hours, orabout 4 hours to about 12 hours, to stabilize the stent, and/orstabilize the crystals and/or terminate crystallization in the polymericmaterial.

In further embodiments, an unannealed or annealed stent is exposed toionizing radiation (e.g., e-beam or gamma radiation) at, above or belowambient temperature, with a single dose or multiple doses of radiationtotaling about 5 kGy to about 100 kGy, or about 10 kGy to about 50 kGy,or about 10 kGy to about 30 kGy, or about 20 kGy to about 60 kGy, orabout 20 kGy to about 40 kGy. In certain embodiments, an unannealed orannealed stent is cooled to reduced temperature (e.g., below 0° C.) andthen is exposed to a single dose or multiple doses of ionizing radiation(e.g., e-beam or gamma radiation) totaling about 10 kGy to about 50 kGy,or about 30 kGy.

The body of the device can be formed from a polymeric material made byany suitable method, such as spraying, dipping, extrusion, molding,injection molding, compression molding, or three-dimensional (3-D)printing, or a combination thereof. In certain embodiments, the body ofthe device is formed from a polymeric article made by spraying asolution or mixture containing at least the biodegradable copolymer orpolymer and at least one solvent onto a structure. When the device is astent, a stent can be laser-cut from a polymeric tube made by sprayingthe polymer solution or mixture onto a mandrel. In another embodiment,the polymeric material or tubular body comprising the biodegradablepolymer is patterned into a stent using (3-D) printing or laser cut. Inanother embodiment, the polymeric material or tubular body comprisingthe biodegradable polymer is formed using extrusion or spraying ordipping, or molding, and is patterned into a stent. In certainembodiments, the stent or body of the device comprises one or moreadditional polymer layers, and/or one or more metal or metal alloylayers, the additional polymer layer(s) of the polymeric material can beformed by spraying additional solution(s) or mixture(s) containing abiodegradable polymer, and/or the metal layer(s) can be formed byapplying metal film(s), foil(s) or tube(s). In some embodiments, apolymer solution or mixture can contain one or more additionalbiodegradable polymers and/or one or more non-degradable polymers, andcan also contain one or more biologically active agents and/or one ormore additives. In another embodiment, the stent or tubular bodycomprises radiopaque markers. Radiopaque markers can be metallic such asgold, platinum, iridium, bismuth, or combination thereof, or alloysthereof. Radiopaque markers can also be polymeric material. Radiopaquemarkers can be incorporated in the stent or tubular body when it isbeing formed or incorporated into the stent or the tubular body afterforming.

In some embodiments, the tubular body or polymeric material or stent maybe formed from at least one polymer having desired degradationcharacteristics where the polymer may be modified to have the desiredcrystallinity, Tg, recoil, strength, shortening, expansioncharacteristics, crimping characteristics, crystallinity, Tg, molecularweight, and/or other characteristics in accordance with the methods ofthe present invention. Polymers include one or more polymers,copolymers, blends, and combination thereof of: Lactides, Glycolides,Caprolactone, Lactides and Glycolides, Lactides and Caprolactones:examples poly-DL-Lactide, polylactide-co-glycolactide;polylactide-co-polycaprolactone, poly (L-lactide-co-trimethylenecarbonate), polylactide-co-caprolactone, polytrimethylene carbonate andcopolymers; polyhydroxybutyrate and copolymers; polyhydroxyvalerate andcopolymers, poly orthoesters and copolymers, poly anhydrides andcopolymers, polyiminocarbonates and copolymers and the like. Aparticularly preferred polymer comprises a copolymer of L-lactide andglycolide, preferably with a weight ratio of 85% L-lactide to 15%glycolide.

In some embodiments, the biodegradable copolymer is selected from thegroup consisting of poly(L-lactide-co-D-lactide),poly(L-lactide-co-D,L-lactide), poly(D-lactide-co-D,L-lactide),poly(lactide-co-glycolide), poly(lactide-co-ε-caprolactone),poly(glycolide-co-ε-caprolactone), poly(lactide-co-dioxanone),poly(glycolide-co-dioxanone), poly(lactide-co-trimethylene carbonate),poly(glycolide-co-trimethylene carbonate), poly(lactide-co-ethylenecarbonate), poly(glycolide-co-ethylene carbonate),poly(lactide-co-propylene carbonate), poly(glycolide-co-propylenecarbonate), poly(lactide-co-2-methyl-2-carboxyl-propylene carbonate),poly(glycolide-co-2-methyl-2-carboxyl-propylene carbonate),poly(3-hydroxybutyrate-co-4-hydroxybutyrate),poly(hydroxybutyrate-co-hydroxyvalerate),poly(3-hydroxybutyrate-co-3-hydroxyvalerate),poly(4-hydroxybutyrate-co-3-hydroxyvalerate),poly(ε-caprolactone-co-fumarate), poly(ε-caprolactone-co-propylenefumarate), poly(lactide-co-ethylene glycol), poly(glycolide-co-ethyleneglycol), poly(ε-caprolactone-co-ethylene glycol),poly(DETOSU-1,6-HD-co-DETOSU-t-CDM),poly(lactide-co-glycolide-co-ε-caprolactone),poly(lactide-co-glycolide-co-trimethylene carbonate),poly(lactide-co-ε-caprolactone-co-trimethylene carbonate),poly(glycolide-co-ε-caprolactone-co-trimethylene carbonate), andpoly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-4-hydroxybutyrate),wherein lactide includes L-lactide, D-lactide and D,L-lactide.

In some embodiments, the biodegradable copolymer is a block or randomcopolymer of D-Lactide, DL-Lactide or L-lactide and ε-caprolactone in aweight or molar ratio of about 70:30 to about 99.9:0.1. In anembodiment, the biodegradable copolymer is a random copolymer ofD-Lactide, DL-Lactide or L-lactide and ε-caprolactone in a weight ormolar ratio of about 90:10, or of about 95:5, or of about 85:15. In anembodiment, the biodegradable copolymer is a random copolymer ofD-Lactide, DL-Lactide or L-lactide and glycolic acid in a weight ormolar ratio of about 70:30 to about 99.9:0.1. In an embodiment, thebiodegradable copolymer is a random copolymer of D-Lactide, DL-Lactideor L-lactide and glycolic acid in a weight or molar ratio of about90:10, or of about 95:5, or of about 85:15.

In some embodiments, the biodegradable copolymer is a block or randomcopolymer of glycolic acid and ε-caprolactone in a weight or molar ratioof about 70:30 to about 99.9:0.1. In an embodiment, the biodegradablecopolymer is a random copolymer of glycolic acid and ε-caprolactone in aweight or molar ratio of about 95:5, or of about 90:10, or of about85:15. In some embodiments, the biodegradable copolymer is a block orrandom copolymer of D-Lactide, DL-Lactide or L-lactide andε-caprolactone and glycolic acid in a weight or molar ratio of about 70%poly lactide:30% (glycolic acid and ε-caprolactone) to about 99% PolyLactide:0.1% (glycolic acid and ε-caprolactone). In an embodiment, thebiodegradable copolymer is a random copolymer of D-Lactide, DL-Lactideor L-Lactide and glycolic acid and ε-caprolactone in a weight or molarratio of about 70:5:25, or of about 85:5:10, or of about 75:20:5.

In yet another embodiment, the stent or the body of the device cancomprise one or more additional biodegradable polymers or co-polymers,and/or one or more additional non-degradable polymers. In yet anotherembodiment, the stent or the body of the device can comprise one or morebiodegradable monomers. These monomers can be same or different typefrom polymer incorporated in the body or stent. Moreover, the stent orbody of the device can comprise one or more biologically active agents,and/or one or more additives such as carbon nano fibers or tubes. Theadditives can serve any of a variety of functions, including controllingdegradation, increasing the strength, increasing elongation, controllingTg, or/and increasing toughness of the material (e.g., polymericmaterial) comprising the body of the device (or the material comprisinga coating on the body), and/or increasing crystallinity.

In further embodiments, the body of the device comprises a layercontaining the biodegradable copolymer, and one or more additionallayers containing a biodegradable polymer or a corrodible metal or metalalloy, wherein the layers can be in any order. The layer containing thebiodegradable copolymer and any additional layer(s) containing abiodegradable polymer can contain one or more additional biodegradablepolymers and/or one or more non-degradable polymers, and can alsocontain one or more biologically active agents and/or one or moreadditives. In further embodiments, the body of the device comprises oneor more layers of the biodegradable copolymer, and optionally one ormore additional layers of a biodegradable polymer same or different or acorrodible metal or metal alloy, wherein the layers can be in any order.The one or more layers of the biodegradable copolymer and optionally theone or more additional layers of a biodegradable polymer (same ordifferent polymer, degradable or non degradable polymer) or a corrodiblemetal or metal alloy optionally may contain one or more biologicallyactive agents and/or one or more additives in one or more of the layers.

In some embodiments, the polylactide copolymer is formed from two ormore different monomers selected from the group consisting ofα-hydroxyacids, L-lactic acid/L-lactide, D-lactic acid/D-lactide,D,L-lactic acid/D,L-lactide, glycolic acid/glycolide, hydroxyalkanoates,hydroxybutyrates, 3-hydroxybutyrate, 4-hydroxybutyrate,hydroxyvalerates, 3-hydroxyvalerate, lactones, ε-caprolactone,δ-valerolactone, β-butyrolactone, β-propiolactone, 1,4-dioxanone(dioxanone), 1,3-dioxanone, carbonates, trimethylene carbonate, ethylenecarbonate, propylene carbonate, 2-methyl-2-carboxylpropylene carbonate,fumarates, propylene fumarate, oxides, ethylene oxide, propylene oxide,anhydrides, orthoesters, DETOSU-1,6HD, DETOSU-t-CDM, ketals and acetals,wherein at least one monomer is L-lactic acid/L-lactide, D-lacticacid/D-lactide or D,L-lactic acid/D,L-lactide. In an embodiment, one ofthe monomers of the polylactide copolymer is L-lactic acid/L-lactide.

In certain embodiments, the polylactide copolymer is selected from thegroup consisting of poly(L-lactide-co-D-lactide),poly(L-lactide-co-D,L-lactide), poly(D-lactide-co-D,L-lactide),poly(lactide-co-glycolide), poly(lactide-co-ε-caprolactone),poly(lactide-co-dioxanone), poly(lactide-co-trimethylene carbonate),poly(lactide-co-ethylene carbonate), poly(lactide-co-propylenecarbonate), poly(lactide-co-2-methyl-2-carboxyl-propylene carbonate),poly(lactide-co-ethylene glycol),poly(lactide-co-glycolide-co-ε-caprolactone),poly(lactide-co-glycolide-co-trimethylene carbonate), andpoly(lactide-co-ε-caprolactone-co-trimethylene carbonate), whereinlactide includes L-lactide, D-lactide and D,L-lactide. In an embodiment,the polylactide copolymer is poly(lactide-co-ε-caprolactone). In anotherembodiment, the polylactide copolymer is poly(lactide-co-glycolide).

The biodegradable implantable device comprising a body comprised of abiodegradable polylactide copolymer can have any features of abiodegradable implantable device comprising a polymeric material or bodycomprised of a biodegradable polymer (including homopolymer orcopolymer) described herein.

In certain embodiments, the biodegradable polymer is selected from thegroup consisting of polyesters, poly(α-hydroxyacids), polylactide,polyglycolide, poly(ε-caprolactone), polydioxanone,poly(hydroxyalkanoates), poly(hydroxypropionates),poly(3-hydroxypropionate), poly(hydroxybutyrates),poly(3-hydroxybutyrate), poly(4-hydroxybutyrate),poly(hydroxypentanoates), poly(3-hydroxypentanoate),poly(hydroxyvalerates), poly(3-hydroxyvalerate),poly(4-hydroxyvalerate), poly(hydroxyoctanoates),poly(3-hydroxyoctanoate), polysalicylate/polysalicylic acid,polycarbonates, poly(trimethylene carbonate), poly(ethylene carbonate),poly(propylene carbonate), tyrosine-derived polycarbonates,L-tyrosine-derived polycarbonates, polyiminocarbonates, poly(DTHiminocarbonate), poly(bisphenol A iminocarbonate), poly(amino acids),poly(ethyl glutamate), poly(propylene fumarate), polyanhydrides,polyorthoesters, poly(DETOSU-1,6HD), poly(DETOSU-t-CDM), polyurethanes,polyphosphazenes, polyamides, nylons, nylon 12, polyoxyethylated castoroil, poly(ethylene glycol), polyvinylpyrrolidone,poly(L-lactide-co-D-lactide), poly(L-lactide-co-D,L-lactide),poly(D-lactide-co-D,L-lactide), poly(lactide-co-glycolide),poly(lactide-co-ε-caprolactone), poly(glycolide-co-ε-caprolactone),poly(lactide-co-dioxanone), poly(glycolide-co-dioxanone),poly(lactide-co-trimethylene carbonate), poly(glycolide-co-trimethylenecarbonate), poly(lactide-co-ethylene carbonate),poly(glycolide-co-ethylene carbonate), poly(lactide-co-propylenecarbonate), poly(glycolide-co-propylene carbonate),poly(lactide-co-2-methyl-2-carboxyl-propylene carbonate),poly(glycolide-co-2-methyl-2-carboxyl-propylene carbonate),poly(lactide-co-hydroxybutyrate), poly(lactide-co-3-hydroxybutyrate),poly(lactide-co-4-hydroxybutyrate), poly(glycolide-co-hydroxybutyrate),poly(glycolide-co-3-hydroxybutyrate),poly(glycolide-co-4-hydroxybutyrate), poly(lactide-co-hydroxyvalerate),poly(lactide-co-3-hydroxyvalerate), poly(lactide-co-4-hydroxyvalerate),poly(glycolide-co-hydroxyvalerate),poly(glycolide-co-3-hydroxyvalerate),poly(glycolide-co-4-hydroxyvalerate),poly(3-hydroxybutyrate-co-4-hydroxybutyrate),poly(hydroxybutyrate-co-hydroxyvalerate),poly(3-hydroxybutyrate-co-3-hydroxyvalerate),poly(3-hydroxybutyrate-co-4-hydroxyvalerate),poly(4-hydroxybutyrate-co-3-hydroxyvalerate),poly(4-hydroxybutyrate-co-4-hydroxyvalerate),poly(ε-caprolactone-co-fumarate), poly(ε-caprolactone-co-propylenefumarate), poly(ester-co-ether), poly(lactide-co-ethylene glycol),poly(glycolide-co-ethylene glycol), poly(ε-caprolactone-co-ethyleneglycol), poly(ester-co-amide), poly(DETOSU-1,6HD-co-DETOSU-t-CDM),poly(lactide-co-cellulose ester), poly(lactide-co-cellulose acetate),poly(lactide-co-cellulose butyrate), poly(lactide-co-cellulose acetatebutyrate), poly(lactide-co-cellulose propionate),poly(glycolide-co-cellulose ester), poly(glycolide-co-celluloseacetate), poly(glycolide-co-cellulose butyrate),poly(glycolide-co-cellulose acetate butyrate),poly(glycolide-co-cellulose propionate),poly(lactide-co-glycolide-co-ε-caprolactone),poly(lactide-co-glycolide-co-trimethylene carbonate),poly(lactide-co-ε-caprolactone-co-trimethylene carbonate),poly(glycolide-co-ε-caprolactone-co-trimethylene carbonate),poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-4-hydroxybutyrate),poly(3-hydroxybutyrate-co-4-hydroxyvalerate-co-4-hydroxybutyrate),collagen, casein, polysaccharides, cellulose, cellulose esters,cellulose acetate, cellulose butyrate, cellulose acetate butyrate,cellulose propionate, chitin, chitosan, dextran, starch, modifiedstarch, and combination thereof, and copolymers thereof, and whereinlactide includes L-lactide, D-lactide and D,L-lactide. In an embodiment,the biodegradable polymer is poly(lactide-co-ε-caprolactone). In anotherembodiment, the biodegradable polymer is poly(lactide-co-glycolide). Inanother embodiment, the biodegradable polymer ispoly(lactide-co-ε-caprolactone), copolymerized or blended/mixed withpoly-glycolide. In another embodiment, the biodegradable polymer ispoly(lactide-co-ε-caprolactone), copolymerized or blended/mixed withpoly-glycolide, and/or carbon nano tubes or fibers. In anotherembodiment, the biodegradable polymer ispoly(lactide-co-ε-caprolactone-co-glycolide) blended, or mixed, withcarbon nano fibers or nanotubes. In yet another embodiment, the polymeris at least one of poly lactide, poly glycolide, and polyε-caprolactone, co-polymerized or mixed with one or more of the othertwo, and/or blended with carbon nano tubes or fibers. One skilled in theart can appreciate that one or more of the embodiments above or part ofthe embodiments above can be combined.

The partially self-expandable biodegradable stent comprising a bodycomprised of a biodegradable polymer can have any features of abiodegradable stent comprising a body comprised of or comprising abiodegradable polymer (including homopolymer or copolymer) describedherein.

Additional embodiments of the disclosure relate to a biodegradable stentcomprising a body comprised of a material, wherein the materialcomprises a biodegradable copolymer of L-lactide and ε-caprolactone in aweight or molar ratio of about 70:30 to about 99.9:0.1. In certainembodiments, the biodegradable copolymer comprises L-lactide andε-caprolactone in a weight or molar ratio of about 90:10. In certainembodiments, the biodegradable copolymer comprises L-lactide andε-caprolactone in a weight or molar ratio of about 99.9:0.1 to about70:30, or about 99:1 to about 80:20, or about 95:5 to about 90:10, orabout 95:5, or about 90:10, or about 85:15, or about 80:20, or about75:25, or about 70:30. In certain embodiments, the biodegradablecopolymer comprises L-lactide and ε-caprolactone in a weight or molarratio of about 99.9:0.1 to about 70:30, or about 99:1 to about 80:20, orabout 95:5 to about 90:10, or about 95:5, or about 90:10, or about85:15, or about 80:20, or about 75:25, or about 70:30 wherein thepolymer (copolymer (or three polymer or more) are substantiallyamorphous, or semicrystalline, or has orientation, or does not haveorientation, or is randomly oriented, or has reduced internal stresses,or has low or no phase separation, or has porosity. In some embodiments,the PLLA/polycaprolactone (PCL) has at least one or more additionalpolymer or copolymer selected from polyglycolic acid (PGA), or/andcarbon nanotube or fibers. This additional agent can enhance strength,ductility, or reduce recoil. The biodegradable stent comprising a bodycomprised of a biodegradable poly(L-lactide-co-ε-caprolactone) copolymeror polymer blend or mixture can have any features of a biodegradablestent comprising a body comprised of a biodegradable polymer (includinghomopolymer or copolymer) described herein.

Non-limiting examples of a biodegradable polymer that can be used toform a biodegradable endoprosthesis or a tubular body thereof, or apolymeric article from which the endoprosthesis or tubular body isformed, include polylactide and copolymers thereof, poly(D,L-lactide),poly(lactide-co-glycolide), poly(lactide-co-ε-caprolactone),poly(lactide-co-trimethylene carbonate), poly(L-lactide-co-trimethylenecarbonate), polytrimethylene carbonate and copolymers thereof,polyhydroxybutyrates and copolymers thereof, polyhydroxyvalerates andcopolymers thereof, polyorthoesters and copolymers thereof,polyanhydrides and copolymers thereof, and polyiminocarbonates andcopolymers thereof, wherein lactide includes L-lactide, D-lactide andD,L-lactide.

In certain embodiments, the biodegradable endoprosthesis, tubular bodyor polymeric article is formed from a poly(L-lactide-co-glycolide)copolymer comprising about 80% to about 90% L-lactide and about 10% toabout 20% glycolide by weight or molarity. In one embodiment, thepoly(L-lactide-co-glycolide) copolymer comprises about 85% L-lactide andabout 15% glycolide by weight or molarity. In further embodiments, thebiodegradable endoprosthesis, tubular body or polymeric article isformed from a poly(L-lactide-co-ε-caprolactone) copolymer comprisingabout 85% to about 95% L-lactide and about 5% to about 15%ε-caprolactone by weight or molarity. In one embodiment, thepoly(L-lactide-co-ε-caprolactone) copolymer comprises about 90%L-lactide and about 10% ε-caprolactone by weight or molarity.

In some embodiments, the biodegradable copolymer or polymer comprisingthe body of the device is derived or formed from, or is comprised of,one, two or more different monomers or polymers selected from the groupconsisting of α-hydroxyacids, L-lactic acid/L-lactide, D-lacticacid/D-lactide, D,L-lactic acid/D,L-lactide, glycolic acid/glycolide,hydroxyalkanoates, hydroxybutyrates, 3-hydroxybutyrate,4-hydroxybutyrate, hydroxyvalerates, 3-hydroxyvalerate,4-hydroxyvalerate, hydroxybenzoic acids, salicylic acid, lactones,ε-caprolactone, δ-valerolactone, β-butyrolactone, β-propiolactone,1,4-dioxanone (dioxanone), 1,3-dioxanone, carbonates, trimethylenecarbonate, ethylene carbonate, propylene carbonate,2-methyl-2-carboxylpropylene carbonate, tyrosine carbonates, L-tyrosinecarbonate, fumarates, propylene fumarate, cellulose esters, celluloseacetate, cellulose butyrate, cellulose acetate butyrate, cellulosepropionate, oxides, ethylene oxide, propylene oxide, anhydrides,orthoesters, DETOSU-1,6HD, DETOSU-t-CDM, ketals, and acetals. In certainembodiments, one of the monomers or polymers of the biodegradablecopolymer or polymer is L-lactic acid/L-lactide. Poly(DETOSU-1,6HD) andpoly(DETOSU-t-CDM) are polyorthoesters based on the diketene acetal3,9-diethylidene-2,4,8,10-tetraoxaspiro[5.5]undecane (DETOSU) and1,6-hexanediol (1,6-HD) or trans-cyclohexanedimethanol (t-CDM).

In certain embodiments, the biodegradable copolymer or polymer isselected from the group consisting of poly(L-lactide-co-D-lactide),poly(L-lactide-co-D,L-lactide), poly(D-lactide-co-D,L-lactide),poly(lactide-co-glycolide), poly(lactide-co-ε-caprolactone),poly(glycolide-co-ε-caprolactone), poly(lactide-co-dioxanone),poly(glycolide-co-dioxanone), poly(lactide-co-trimethylene carbonate),poly(glycolide-co-trimethylene carbonate), poly(lactide-co-ethylenecarbonate), poly(glycolide-co-ethylene carbonate),poly(lactide-co-propylene carbonate), poly(glycolide-co-propylenecarbonate), poly(lactide-co-2-methyl-2-carboxyl-propylene carbonate),poly(glycolide-co-2-methyl-2-carboxyl-propylene carbonate),poly(lactide-co-hydroxybutyrate), poly(lactide-co-3-hydroxybutyrate),poly(lactide-co-4-hydroxybutyrate), poly(glycolide-co-hydroxybutyrate),poly(glycolide-co-3-hydroxybutyrate),poly(glycolide-co-4-hydroxybutyrate), poly(lactide-co-hydroxyvalerate),poly(lactide-co-3-hydroxyvalerate), poly(lactide-co-4-hydroxyvalerate),poly(glycolide-co-hydroxyvalerate),poly(glycolide-co-3-hydroxyvalerate),poly(glycolide-co-4-hydroxyvalerate),poly(3-hydroxybutyrate-co-4-hydroxybutyrate),poly(hydroxybutyrate-co-hydroxyvalerate),poly(3-hydroxybutyrate-co-3-hydroxyvalerate),poly(3-hydroxybutyrate-co-4-hydroxyvalerate),poly(4-hydroxybutyrate-co-3-hydroxyvalerate),poly(4-hydroxybutyrate-co-4-hydroxyvalerate),poly(ε-caprolactone-co-fumarate), poly(ε-caprolactone-co-propylenefumarate), poly(lactide-co-ethylene glycol), poly(glycolide-co-ethyleneglycol), poly(ε-caprolactone-co-ethylene glycol),poly(DETOSU-1,6-HD-co-DETOSU-t-CDM), poly(lactide-co-cellulose ester),poly(lactide-co-cellulose acetate), poly(lactide-co-cellulose butyrate),poly(lactide-co-cellulose acetate butyrate), poly(lactide-co-cellulosepropionate), poly(glycolide-co-cellulose ester),poly(glycolide-co-cellulose acetate), poly(glycolide-co-cellulosebutyrate), poly(glycolide-co-cellulose acetate butyrate),poly(glycolide-co-cellulose propionate),poly(lactide-co-glycolide-co-ε-caprolactone),poly(lactide-co-glycolide-co-trimethylene carbonate),poly(lactide-co-ε-caprolactone-co-trimethylene carbonate),poly(glycolide-co-ε-caprolactone-co-trimethylene carbonate),poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-4-hydroxybutyrate), andpoly(3-hydroxybutyrate-co-4-hydroxyvalerate-co-4-hydroxybutyrate),wherein lactide includes L-lactide, D-lactide and D,L-lactide.

In some embodiments, the biodegradable copolymer is a polylactidecopolymer, wherein lactide includes L-lactide, D-lactide andD,L-lactide. In certain embodiments, the biodegradable copolymer is apoly(L-lactide) copolymer. The poly(L-lactide) copolymer can compriseL-lactide and one or more other monomers selected from any of themonomers described herein. In certain embodiments, the biodegradablecopolymer is selected from the group consisting ofpoly(L-lactide-co-D-lactide), poly(L-lactide-co-D,L-lactide),poly(L-lactide-co-glycolide), poly(L-lactide-co-ε-caprolactone),poly(L-lactide-co-dioxanone), poly(L-lactide-co-3-hydroxybutyrate),poly(L-lactide-co-4-hydroxybutyrate),poly(L-lactide-co-4-hydroxyvalerate), poly(L-lactide-co-ethylenecarbonate), poly(L-lactide-co-propylene carbonate),poly(L-lactide-co-trimethylene carbonate), andpoly(L-lactide-co-cellulose acetate butyrate).

In some embodiments, the biodegradable poly(L-lactide) copolymer orpolymer comprises L-lactide or D-Lactide or DL-Lactide in at least about70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% byweight or molarity, and each of the one or more other monomers orpolymers in no more than about 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%,4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25% or 30% by weight ormolarity. In certain embodiments, the biodegradable poly(L-lactide)copolymer or polymer comprises L-lactide or D-Lactide or DL-Lactide inat least about 90%, 95% or 99% by weight or molarity, and each of theone or more other monomers or polymers in no more than about 1%, 5% or10% by weight or molarity.

In further embodiments, the biodegradable copolymer ispoly(lactide-co-ε-caprolactone). In certain embodiments, thebiodegradable copolymer is a block or random copolymer of L-Lactide orD-Lactide or DL-Lactide and ε-caprolactone in a weight or molar ratio ofabout 70:30 to about 99.9:0.1, or about 80:20 to about 99:1, or about85:15 to about 99:1, or about 85:15 to about 95:5, or about 87:13 toabout 93:7, or about 90:10. In an embodiment, the biodegradablecopolymer is a random copolymer of L-lactide or D-Lactide or DL-Lactideand ε-caprolactone in a weight or molar ratio of about 90:10. In anembodiment, the biodegradable polymer is a blend or mixture of L-lactideor D-Lactide or DL-Lactide and ε-caprolactone in a weight or molar ratioof about 70:30 to about 99.9:0.1.

In other embodiments, the biodegradable copolymer ispoly(lactide-co-glycolide). In certain embodiments, the biodegradablecopolymer is a block or random copolymer of L-Lactide or D-Lactide orDL-Lactide and glycolide in a weight or molar ratio of about 70:30 toabout 99:1, or about 75:25 to about 95:5, or about 80:20 to about 90:10,or about 82:18 to about 88:12, or about 85:15. In an embodiment, thebiodegradable copolymer is a random copolymer of L-lactide or D-Lactideor DL-Lactide and glycolide in a weight or molar ratio of about 85:15.

In additional embodiments, the body of the device, or the materialcomprising or comprising the body of the device, comprises thebiodegradable polymer or copolymer, and a second biodegradable polymeror a non-degradable polymer or both. The non-degradable polymer can beany non-degradable polymer described herein. The amount of thenon-degradable polymer used can be selected to provide the device withdesired characteristics while not extending the degradation time of thedevice beyond the desired time period. In certain embodiments, the nondegradable polymer is selected from the group consisting ofpolyacrylates, polymethacrylates, poly(n-butyl methacrylate),poly(hydroxyethylmethacrylate), polyamides, nylons, nylon 12,poly(ethylene glycol), polydimethylsiloxane, polyvinylpyrrolidone,phosphorylcholine-containing polymers,poly(2-methacryloyloxyethylphosphorylcholine),poly(2-methacryloyloxyethylphosphorylcholine-co-butyl methacrylate), andpolymers or copolymers thereof.

The second biodegradable polymer can be any biodegradable polymer orcopolymer described herein. In some embodiments, the secondbiodegradable polymer is selected from the group consisting ofpolyesters, poly(α-hydroxyacids), polylactide including L-Lactides,D-Lactide, and DL-Lactide, polyglycolide, poly(ε-caprolactone),polydioxanone, poly(hydroxyalkanoates), poly(hydroxypropionates),poly(3-hydroxypropionate), poly(hydroxybutyrates),poly(3-hydroxybutyrate), poly(4-hydroxybutyrate),poly(hydroxypentanoates), poly(3-hydroxypentanoate),poly(hydroxyvalerates), poly(3-hydroxyvalerate),poly(4-hydroxyvalerate), poly(hydroxyoctanoates),poly(3-hydroxyoctanoate), polysalicylate/polysalicylic acid,polycarbonates, poly(trimethylene carbonate), poly(ethylene carbonate),poly(propylene carbonate), tyrosine-derived polycarbonates,L-tyrosine-derived polycarbonates, polyiminocarbonates, poly(DTHiminocarbonate), poly(bisphenol A iminocarbonate), poly(amino acids),poly(ethyl glutamate), poly(propylene fumarate), polyanhydrides,polyorthoesters, poly(DETOSU-1,6HD), poly(DETOSU-t-CDM), polyurethanes,polyphosphazenes, polyamides, nylons, nylon 12, polyoxyethylated castoroil, poly(ethylene glycol), polyvinylpyrrolidone,poly(L-lactide-co-D-lactide), poly(L-lactide-co-D,L-lactide),poly(D-lactide-co-D,L-lactide), poly(lactide-co-glycolide),poly(lactide-co-ε-caprolactone), poly(glycolide-co-ε-caprolactone),poly(lactide-co-dioxanone), poly(glycolide-co-dioxanone),poly(lactide-co-trimethylene carbonate), poly(glycolide-co-trimethylenecarbonate), poly(lactide-co-ethylene carbonate),poly(glycolide-co-ethylene carbonate), poly(lactide-co-propylenecarbonate), poly(glycolide-co-propylene carbonate),poly(lactide-co-2-methyl-2-carboxyl-propylene carbonate),poly(glycolide-co-2-methyl-2-carboxyl-propylene carbonate),poly(lactide-co-hydroxybutyrate), poly(lactide-co-3-hydroxybutyrate),poly(lactide-co-4-hydroxybutyrate), poly(glycolide-co-hydroxybutyrate),poly(glycolide-co-3-hydroxybutyrate),poly(glycolide-co-4-hydroxybutyrate), poly(lactide-co-hydroxyvalerate),poly(lactide-co-3-hydroxyvalerate), poly(lactide-co-4-hydroxyvalerate),poly(glycolide-co-hydroxyvalerate),poly(glycolide-co-3-hydroxyvalerate),poly(glycolide-co-4-hydroxyvalerate),poly(3-hydroxybutyrate-co-4-hydroxybutyrate),poly(hydroxybutyrate-co-hydroxyvalerate),poly(3-hydroxybutyrate-co-3-hydroxyvalerate),poly(3-hydroxybutyrate-co-4-hydroxyvalerate),poly(4-hydroxybutyrate-co-3-hydroxyvalerate),poly(4-hydroxybutyrate-co-4-hydroxyvalerate),poly(ε-caprolactone-co-fumarate), poly(ε-caprolactone-co-propylenefumarate), poly(ester-co-ether), poly(lactide-co-ethylene glycol),poly(glycolide-co-ethylene glycol), poly(ε-caprolactone-co-ethyleneglycol), poly(ester-co-amide), poly(DETOSU-1,6HD-co-DETOSU-t-CDM),poly(lactide-co-cellulose ester), poly(lactide-co-cellulose acetate),poly(lactide-co-cellulose butyrate), poly(lactide-co-cellulose acetatebutyrate), poly(lactide-co-cellulose propionate),poly(glycolide-co-cellulose ester), poly(glycolide-co-celluloseacetate), poly(glycolide-co-cellulose butyrate),poly(glycolide-co-cellulose acetate butyrate),poly(glycolide-co-cellulose propionate),poly(lactide-co-glycolide-co-ε-caprolactone),poly(lactide-co-glycolide-co-trimethylene carbonate),poly(lactide-co-ε-caprolactone-co-trimethylene carbonate),poly(glycolide-co-ε-caprolactone-co-trimethylene carbonate),poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-4-hydroxybutyrate),poly(3-hydroxybutyrate-co-4-hydroxyvalerate-co-4-hydroxybutyrate),collagen, casein, polysaccharides, cellulose, cellulose esters,cellulose acetate, cellulose butyrate, cellulose acetate butyrate,cellulose propionate, chitin, chitosan, dextran, starch, modifiedstarch, and copolymers thereof, wherein lactide includes L-lactide,D-lactide and D,L-lactide. Poly(DTH iminocarbonate) is a polymer of thedesaminotyrosyl-tyrosine hexyl ester (DTH) iminocarbonate. In someembodiments, the second biodegradable polymer is a polylactidehomopolymer or copolymer, wherein lactide includes L-lactide, D-lactideand D,L-lactide. In certain embodiments, the second biodegradablepolymer is a poly(L-lactide) homopolymer or copolymer.

In certain embodiments, the second biodegradable polymer is selectedfrom the group consisting of poly(L-lactide), poly(D-lactide),poly(D,L-lactide), polyglycolide, poly(ε-caprolactone), polydioxanone,poly(L-lactide-co-glycolide), poly(D-lactide-co-glycolide),poly(D,L-lactide-co-glycolide), poly(L-lactide-co-ε-caprolactone),poly(D-lactide-co-ε-caprolactone), poly(D,L-lactide-co-ε-caprolactone),poly(glycolide-co-ε-caprolactone), poly(L-lactide-co-trimethylenecarbonate), poly(D-lactide-co-trimethylene carbonate),poly(D,L-lactide-co-trimethylene carbonate),poly(glycolide-co-trimethylene carbonate), poly(DTH iminocarbonate),poly(bisphenol A iminocarbonate), poly(DETOSU-1,6HD-co-DETOSU-t-CDM),and a combination thereof.

In some embodiments, the body of the device, or the material comprisingthe body of the device, comprises a blend of the biodegradablecopolymer, and a second biodegradable polymer or a non-degradablepolymer or both. In certain embodiments, the body of the device, or thematerial comprising the body of the device, comprises a blend of a blockor random copolymer of L-lactide or D-Lactide or DL-Lactide andε-caprolactone in a weight or molar ratio of about 70:30 to about99.9:0.1 and a different block or random copolymer of L-lactide orD-Lactide or DL-Lactide and ε-caprolactone in a weight or molar ratio ofabout 70:30 to about 99.9:0.1; or a blend of a block or random copolymerof L-lactide or D-Lactide or DL-Lactide and ε-caprolactone in a weightor molar ratio of about 85:15 to about 99.9:0.1 and a different block orrandom copolymer of L-lactide or D-Lactide or DL-Lactide andε-caprolactone in a weight or molar ratio of about 85:15 to about99.9:0.1; or a blend of a block or random copolymer of L-lactide orD-Lactide or DL-Lactide and ε-caprolactone in a weight or molar ratio ofabout 70:30 to about 90:10 and a different block or random copolymer ofL-lactide or D-Lactide or DL-Lactide and ε-caprolactone in a weight ormolar ratio of about 90:10 to about 99:1; or a blend of a block orrandom copolymer of L-lactide or D-Lactide or DL-Lactide andε-caprolactone in a weight or molar ratio of about 85:15 to about 90:10and a different block or random copolymer of L-lactide or D-Lactide orDL-Lactide and ε-caprolactone in a weight or molar ratio of about 90:10to about 95:5; or a blend of about 85:15 block or randompoly(lactide-co-ε-caprolactone) such aspoly(L-lactide-co-ε-caprolactone) and about 95:5 block or randompoly(lactide-co-ε-caprolactone) such aspoly(L-lactide-co-ε-caprolactone); or a blend of a block or randomcopolymer of L-lactide or D-Lactide or DL-Lactide and ε-caprolactone ina weight or molar ratio of about 85:15 to about 99:1, with about 85:15block or random poly(lactide-co-ε-caprolactone) such aspoly(L-lactide-co-ε-caprolactone), or about 90:10 block or randompoly(lactide-co-ε-caprolactone) such aspoly(L-lactide-co-ε-caprolactone), or about 95:5 block or randompoly(lactide-co-ε-caprolactone) such aspoly(L-lactide-co-ε-caprolactone), or poly(ε-caprolactone), orpolylactide, or polyglycolide, or polydioxanone, orpoly(hydroxybutyrate), or poly(hydroxyvalerate), or poly(trimethylenecarbonate), or poly(ethylene carbonate), or poly(propylene carbonate),or poly(DTH iminocarbonate), or poly(bisphenol A iminocarbonate), orpoly(lactide-co-glycolide), or poly(lactide-co-trimethylene carbonate),or poly(glycolide-co-trimethylene carbonate), orpoly(glycolide-co-ε-caprolactone), orpoly(DETOSU-1,6HD-co-DETOSU-t-CDM), or a combination thereof, whereinlactide includes L-lactide, D-lactide and D,L-lactide.

In further embodiments, the body of the device comprises a first layercontaining the biodegradable copolymer or polymer, and one, two, three,four or more additional layers, wherein each additional layer contains abiodegradable polymer or a corrodible metal or metal alloy, and whereinthe first layer and the additional layer(s) can be in any order. Thebiodegradable polymer that can compose any additional layer(s) canindependently be any biodegradable polymer described herein. The firstlayer containing the biodegradable copolymer and any additional layer(s)containing a biodegradable polymer can each optionally and independentlycontain an additional biodegradable polymer or a non-degradable polymeror both. The additional biodegradable polymer that can optionallycompose the first layer and any additional layer(s) can independently beany biodegradable polymer described herein, and the non-degradablepolymer that can optionally compose the first layer and any additionallayer(s) can independently be any non-degradable polymer describedherein.

Non-limiting examples of corrodible metals and metal alloys that canindependently comprise any additional layer(s) of the body of the deviceinclude cast ductile irons (e.g., 80-55-06 grade cast ductile iron),corrodible steels (e.g., AISI 1010 steel, AISI 1015 steel, AISI 1430steel, AISI 5140 steel and AISI 8620 steel), melt-fusible metal alloys,bismuth-tin alloys (e.g., 40% bismuth-60% tin and 58% bismuth-42% tin),bismuth-tin-indium alloys, magnesium alloys, tungsten alloys, zincalloys, shape-memory metal alloys, and superelastic metal alloys.

If the body of the device contains multiple layers, each layer can beselected to have certain characteristics based on its composition sothat the device has desired overall characteristics. For example, thematerial comprising a particular layer can be selected to have certaincharacteristics (e.g., strength, toughness, ductility, degradation rate,etc.) by containing certain biodegradable polymer(s), and optionallycertain nondegradable polymer(s) and certain additive(s), and certainamount thereof, where the characteristics of that material can besubstantially similar to or different from the characteristics of thematerial comprising each of the other layer(s). As a non-limitingexample, the body of the device can comprise a middle one or morelayer(s) containing a high-strength material, e.g., a high-strengthpolymer, such as poly(L-lactide) or a copolymer thereof] and inner andouter layer(s) containing a ductile material, e.g., a ductile polymer,such as poly(ε-caprolactone), such that the device possesses sufficientstrength, flexibility and toughness.

In some embodiments, the biodegradable copolymer, optional secondbiodegradable polymer, optional additional biodegradable polymer(s), oroptional non-degradable polymer(s), or any combination thereof,comprising the body of the device are crosslinked. In certainembodiments, the polymer(s) are crosslinked by exposure to radiation(e.g., ultraviolet (UV) light, or ionizing radiation, such as e-beam orgamma radiation), exposure to heat, use of a degradable ornon-degradable crosslinker, or use of a crosslinking agent and aninitiator.

In certain embodiments, the degradable or non-degradable crosslinker isselected from the group consisting of diisocyanates, methylene diphenyldiisocyanates, tetramethylenediisocyanate, pentamethylenediisocyanate,hexamethylenediisocyanate, disuccinimidyl glutarate, disuccinimidylsuberate, bis(succinimidoxycarbonyl)poly(ethylene glycol),bis(2-[succinimidoxycarbonyloxy]ethyl)sulfone,tris(2-succinimidoxycarbonylethyl)-amine, multi-armed poly(ethyleneglycol), dipentaerythritol, tripentaerythritol, pentaerythritolethoxylate, pentaerythritol propoxylate, methyl silyl ethercrosslinkers, ethyl silyl ether crosslinkers, propyl silyl ethercrosslinkers, isopropyl silyl ether crosslinkers, butyl silyl ethercrosslinkers, and tert-butyl silyl ether crosslinkers.

In some embodiments, the crosslinking agent is selected from the groupconsisting of maleic anhydride, 1,2-bis(maleimido)ethane,1,4-bis(maleimido)butane, 1,6-bis(maleimido)hexane,1,8-bis(maleimido)diethylene glycol, and tris(2-maleimidoethyl)amine. Incertain embodiments, the initiator is selected from the group consistingof organic peroxides, di-tert-butyl peroxide, dicumyl peroxide, benzoylperoxide, methyl ethyl ketone peroxide, azo compounds,1,1′-azobis(cyclohexanecarbonitrile), and 1,1′-azobis(isobutyronitrile).

Further embodiments of the disclosure relate to a biodegradableimplantable device comprising a body comprising a material whichcomprises a blend of polymers, wherein the blend includes abiodegradable polymer, and an additional biodegradable polymer or anon-degradable polymer or both. The biodegradable polymer and theadditional biodegradable polymer can be any biodegradable polymerdescribed herein, and the non-degradable polymer can be anynon-degradable polymer described herein. The amount of anynon-degradable polymer utilized can be selected to impart desiredcharacteristics (e.g., strength) to the material or the device withoutprolonging the degradation time of the device over a certain length oftime. Embodiments herein relating to a biodegradable implantable devicecomprising a polymeric material or body comprised of a material whichcomprises a biodegradable copolymer also relate to a biodegradableimplantable device comprising a body comprised of a material whichcomprises a blend of polymers, where a blend of polymers can substitutefor a biodegradable copolymer in such embodiments.

In some embodiments, the biodegradable implantable device comprisespolymeric material or a body comprising a material which comprisesPoly(Lactide) such as poly(L-lactide) or a poly(L-lactide) copolymer,and an additional biodegradable polymer or a non-degradable polymer orboth. The poly(L-lactide) copolymer can be any poly(L-lactide) copolymerdescribed herein. In certain embodiments, the material comprising thebody of the device comprises poly(L-lactide) and poly(ε-caprolactone).In some embodiments, the weight percent of poly(L-lactide) or thepoly(L-lactide) copolymer in the material comprising the body of thedevice is at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%,99%, 99.5% or 99.9%, and the weight percent of each of the additionalbiodegradable polymer and/or the non-degradable polymer is no more thanabout 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%,8%, 9%, 10%, 15%, 20%, 25% or 30%. In certain embodiments, the weightpercent of poly(L-lactide) or the poly(L-lactide) copolymer in thematerial comprising the body of the device is at least about 90%, 95% or99%, and the weight percent of each of the additional biodegradablepolymer and/or the non-degradable polymer is no more than about 1%, 5%or 10%.

Examples of biodegradable polymers that can be used to formbiodegradable endoprostheses (e.g., stents) include without limitationpolylactide, poly(trimethylene carbonate), poly(lactide-co-glycolide),poly(lactide-co-ε-caprolactone), poly(lactide-co-trimethylenecarbonate), polyhydroxybutyrates, polyhydroxyvalerates, polyorthoesters,polyanhydrides, polyiminocarbonates, and copolymers, blends andcombinations thereof, wherein lactide includes L-lactide, D-lactide andD,L-lactide. In some embodiments, the polymeric material or the body ofa biodegradable endoprosthesis is comprises a polylactide homopolymer orcopolymer, wherein lactide includes L-lactide, D-lactide andD,L-lactide. In certain embodiments, the body of the biodegradableendoprosthesis comprises a poly(L-lactide) homopolymer or copolymer.

In some embodiments, a biodegradable endoprosthesis comprisespoly(L-lactide-co-glycolide) copolymer or polymer comprising about 80%to about 90% L-lactide and about 10% to about 20% glycolide by weight ormolarity. In an embodiment, the poly(L-lactide-co-glycolide) copolymeror polymer comprises about 85% L-lactide and about 15% glycolide byweight or molarity. In further embodiments, a biodegradableendoprosthesis is formed from a poly(L-lactide-co-ε-caprolactone)copolymer or polymer comprising about 85% to about 95% L-lactide andabout 5% to about 15% ε-caprolactone by weight or molarity. In anembodiment, the poly(L-lactide-co-ε-caprolactone) copolymer or polymercomprises about 90% L-lactide and about 10% ε-caprolactone by weight ormolarity.

Additional examples of biodegradable polymers that can be used to formbiodegradable endoprostheses (e.g., stents) include without limitationpolyesters, polyanhydrides, polyalkylene carbonates,polyiminocarbonates, polyorthoesters, poly(ether esters), polyamides,poly(ester amides), polyamines, poly(ester amines), polyurethanes,poly(ester urethanes), polyureas, poly(ethylene imines),polyphosphazenes, polyphosphates, polyphosphonates, polysulfonates,polysulfonamides, polyethers, polyacrylic acids, polycyanoacrylates,polyvinylacetate, polylactide, polyglycolide, poly(malic acid),poly(L-lactic acid-co-D,L-lactic acid), poly(lactide-co-glycolide),poly(ε-caprolactone), polydioxanone, poly(trimethylene carbonate),poly(ethylene carbonate), poly(propylene carbonate), poly(ethylenecarbonate-co-trimethylene carbonate), poly(lactic acid-co-trimethylenecarbonate), poly(L-lactic acid-co-trimethylene carbonate-co-D,L-lacticacid), poly(glycolic acid-co-trimethylene carbonate),poly(ε-caprolactone-co-trimethylene carbonate), poly(glycolicacid-co-trimethylene carbonate-co-dioxanone), polyhydroxybutyrates,polyhydroxyvalerates, poly(3-hydroxybutyrate-co-hydroxyvalerate),poly(ethyl glutamate), modified poly(ethylene terephthalate),poly(butylene succinate), poly(butylene succinate adipate),poly(butylene succinate terephthalate), poly(butyleneadipate-co-terephthalate), starch-based polymers, hyaluronic acid,regenerated cellulose, oxidized and non-oxidized regenerated cellulosecopolymers, and copolymers, blends and combinations thereof, whereinlactic acid/lactide includes L-lactic acid/L-lactide, D-lacticacid/D-lactide and D,L-lactic acid/D,L-lactide.

The biodegradable polymers can be homopolymers, block copolymers, randomcopolymers, graft copolymers, polymers having functional groups (e.g.,acidic, basic, hydrophilic, amino, hydroxyl, thiol, and/or carboxylgroups) along the backbone and/or at the ends, or a blend of two or morehomopolymers and/or copolymers. In certain embodiments, the body of abiodegradable endoprosthesis is comprised of a random copolymer. Incertain embodiments, the body of a biodegradable endoprosthesis iscomprised of a biodegradable blend or mixture of polymers. In yetanother embodiment, the biodegradable polymer comprises one or morepolymers.

The polymeric material/article and/or the tubular body and/or theprosthesis or device can undergo any of a variety of modification ortreatments (e.g., longitudinal extension, radial expansion, heating,cooling, quenching, pressurizing, vacuuming, exposure/incorporation ofsolvents, incorporation of additive, removal of additives or impurities,or exposure to radiation or carbon dioxide, or a combination thereof)designed to control or enhance characteristics (e.g., crystallinity,strength, toughness and degradation, Tg, recoil, shortening, expansion)of the article, the tubular body, and/or the prosthesis or device. Thebiodegradable implantable device comprising a polymeric polymer(including homopolymer or copolymer) described herein.

In certain embodiments, the modification comprises annealing/heating thebiodegradable polymer (e.g., tubular body), wherein the biodegradablepolymer or co-polymer or tubular body or stent is heated to atemperature at about Tg, or below Tg from about 1° C. to about 50° C.below Tg, or from about 5° C. to about 25° C. below Tg, or from about10° C. to about 15° C. below Tg, or above the glass transitiontemperature (T_(g)) of the polymeric material and below the meltingpoint (T_(m)) of the polymeric material for a period of time (e.g.,about one minute to about three hours, at one temperature, or more thanone temperature in controlled increments), or to a temperature to meltthe material, or to a temperature that is of about 1° C.-70° C. aboveTg, or about 5° C.-50° C. above Tg, or about 10° C.-40° C. above Tg, orabout 15-30° C. above Tg; and then is slowly or quickly cooled orquenched to a lower temperature, e.g., to ambient temperature or lower,or to about −80° C. to about 30° C. or about −20° C. to about 25° C., orabout 0° C. to about 25° C., in about 5 seconds to 2 hours or about afraction of a second to 5 hours. Either before or after being annealed,the biodegradable polymer (tube) can be patterned into an endoprosthesisstructure (e.g., a structure capable of radial contraction andexpansion, such as a stent) by laser cutting or other method known inthe art. Exemplary stent patterns are described in U.S. patentapplication Ser. No. 12/016,077, whose entire disclosure is incorporatedherein by reference. Alternatively, the tubular body can be annealedboth before and after being patterned into an endoprosthesis structure,or additional annealing steps can be performed so that the biodegradablepolymer tube can be subjected to two, three, four or more annealingsteps during the fabrication process. In other embodiments, theannealing temperature is about 50° C. below Tg to about Tg, or 35° C.below Tg to about Tg, or about 20° C. below Tg to about Tg, or about 10°C. below Tg to about Tg, Or about 20° C. to about 45° C. In a thirdembodiment, an annealing of the tubular body or the stent is performedpost radiation or sterilization at a temperature ranging from about 20°C. to about 80° C., or from about 25° C. to about 50° C., or from about25° C. to about 35° C.; for about 1 minute to about 7 days, or for about10 minutes to about 3 days, or for about 1 hour to about 1 day.

A polymeric material can be made into an article (e.g., a tube) byspraying, dipping, extrusion, molding, injection molding, compressionmolding, 3-D printing or other process. The polymeric article or tubecan be placed under vacuum (e.g., about −25 in. Hg or lower) and/orheated to remove any residual solvents and monomers, and then can beannealed and quenched to increase crystallinity (e.g., degree ofcrystallinity) of the polymeric material and/or reduce residual orinternal stress in the polymeric article or tube. In some embodiments,the polymeric article or tube is placed under vacuum (e.g., at about 1torr or below) and/or is heated at temperature ranging from below Tg,about Tg, or above Tg, or at elevated temperature (e.g., at about 40° C.or above) to remove any residual water, solvents and monomers, and isthen annealed by being heated to a temperature below Tg, about Tg, orabove the glass transition temperature (T_(g)) and below the meltingtemperature (T_(m)) of the polymeric material. In certain embodiments,the annealing temperature is at least about 1° C., 5° C., 10° C., 20°C., 30° C., 40° C. or 50° C. higher than the T_(g), and is at leastabout 1° C., 5° C., 10° C., 20° C., 30° C., 40° C., 50° C., 75° C. or100° C. lower than the T_(m) of the polymeric material. In anembodiment, the annealing temperature is at least about 10° C. above theT_(g) and is at least about 20° C. below the T_(m) of the polymericmaterial. In certain embodiments, the annealing time is about 1 minuteto about 10 days, or about 5 or 30 minutes to about 1 day, or about 15or 30 minutes to about 12 hours, or about 15 or 30 minutes to about 6hours, or about 15 or 30 minutes to about 3 hours, or about 1 hour toabout 6 hours, or about 1 hour to about 3 hours, or about 1.5 hours toabout 2.5 hours. In an embodiment, the annealing time is about 30minutes to about 6 hours.

In some embodiments, the polymeric article undergoes one or more cyclesof annealing involving heating and cooling, which can, e.g., increasethe strength of the material (e.g., polymeric material), reduce residualor internal stress in the polymeric article, and/or control itscrystallinity, including its degree of crystallinity and the size,number and distribution of crystals or crystalline regions in thematerial (e.g., polymeric material). In certain embodiments, thepolymeric article is heated at a temperature equal to or greater thanthe glass transition temperature (T_(g)) of the first biodegradablepolymer or the material (e.g., polymeric material) comprising thepolymeric article for a period of time (e.g., at least about 0.1, 0.25,0.5, 1, 4, 8, 12 or 24 hours), and then quickly or slowly cooled to alower temperature (e.g., at least about 10° C., 20° C., 30° C., 40° C.or 50° C. below the T_(g), or to ambient temperature or below) over aperiod of time (e.g., about 10 sec, 30 sec, 1 min, 10 min, 30 min, 1 hr,4 hr, 8 hr or 12 hr). In further embodiments, the polymeric article isheated at a temperature above the T_(g) and below the meltingtemperature (T_(m)) of the first biodegradable polymer or the material(e.g., polymeric material) comprising the polymeric article for a periodof time (e.g., at least about 0.1, 0.25, 0.5, 1, 4, 8, 12 or 24 hours),and then cooled to a lower temperature (e.g., at least about 10° C., 20°C., 30° C., 40° C. or 50° C. below the T_(g), or to ambient temperatureor below) over a period of time (e.g., about 10 sec, 30 sec, 1 min, 10min, 30 min, 1 hr, 4 hr, 8 hr or 12 hr). In certain embodiments, thepolymeric article is heated at a temperature within the coldcrystallization temperature range of the first biodegradable polymer orthe material (e.g., polymeric material) comprising the polymeric articlefor a period of time (e.g., at least about 0.1, 0.25, 0.5, 1, 4, 8, 12or 24 hours), and then cooled to a lower temperature (e.g., at leastabout 10° C., 20° C., 30° C., 40° C. or 50° C. below the T_(g), or toambient temperature or below) over a period of time (e.g., about 10 sec,30 sec, 1 min, 10 min, 30 min, 1 hr, 4 hr, 8 hr or 12 hr). In stillfurther embodiments, the polymeric article is heated at a temperatureequal to or greater than the T_(m) of the first biodegradable polymer orthe material (e.g., polymeric material) comprising the polymeric articlefor a period of time (e.g., at least about 0.1, 0.25, 0.5, 1, 4, 8, 12or 24 hours) to melt crystalline regions of the first biodegradablepolymer or the material (e.g., polymeric material), and then cooled to alower temperature (e.g., at least about 10° C., 20° C., 30° C., 40° C.or 50° C. below the T_(g), or to ambient temperature or below) over aperiod of time (e.g., about 10 sec, 30 sec, 1 min, 10 min, 30 min, 1 hr,4 hr, 8 hr or 12 hr).

In one preferred embodiment, the polymeric material is treated whereinthe treatment comprises inducing or incorporation of monomers orpolymers including co-polymers wherein the one or more monomers orpolymers amounts in the polymeric material or the stent after treatmentranges from 0.001% to 10% by weight, preferably ranges from 0.1% to 5%by weight, more preferably ranges from 0.1% to 3% by weight. In onepreferred embodiment, the polymeric material is treated wherein thetreatment comprises inducing or incorporation of monomers or polymerswherein the one or more monomers or polymers amounts in the polymericmaterial or the stent after treatment ranges from 0.001% to 10% byweight, preferably ranges from 0.1% to 5% by weight, more preferablyranges from 0.1% to 3% by weight and wherein the stent at bodytemperature is capable to expand from a crimped configuration to adeployed diameter without fracture and have sufficient strength tosupport a body lumen. In one preferred embodiment, the polymericmaterial is treated wherein the treatment comprises inducing orincorporation of monomers or polymers wherein the one or more monomersor polymers amounts in the polymeric material or the stent aftertreatment ranges from 0.001% to 10% by weight, preferably ranges from0.1% to 5% by weight, more preferably ranges from 0.1% to 3% by weightand wherein the one or more monomers or polymers substantially does notaffect degradation of the stent (preferably does not affect degradationthe stent. In other embodiments the monomer opr polymer acceleratesdegradation of the stent) and wherein the stent at body temperature iscapable to expand from a crimped configuration to a deployed diameterwithout fracture and have sufficient strength to support a body lumen.In one preferred embodiment, the polymeric material is treated whereinthe treatment comprises inducing or incorporation of monomer or polymerwherein the one or more monomer or polymer amounts in the polymericmaterial or the stent after treatment ranges from 0.001% to 10% byweight, preferably ranges from 0.1% to 5% by weight, more preferablyranges from 0.1% to 3% by weight and wherein the one or more monomer orpolymer preferably substantially does not affect the stent degradation(preferably accelerates the stent degradation) and wherein the one ormore monomer or polymer substantially remains in the stent in the rangesdescribed above before deployment of the stent) wherein the stent atbody temperature is capable to expand from a crimped configuration to adeployed diameter without fracture and have sufficient strength tosupport a body lumen. In another preferred embodiment, the one or moremonomer or polymer amounts are greater than 0.1%, preferably greaterthan 1%, more preferably greater than 3%, more preferably greater than5% by weight of the polymeric material. Examples of monomers or polymersinclude lactides, glycolides, caprolactones, lactides and glycolides,lactides and caprolactones to name a few. Incorporation of monomers cantake place, for example by spraying as described herein, or inducing byradiation. Preferred Tg ranges from 20° C. to 50° C., more preferredfrom greater than 37° C. to less than 50° C. Preferred crystallinityranges from 1% to 60%, preferably from 1% to 55%, more preferably from1% to 45%, most preferably from 1% to 35%. The polymeric materialpreferably has an initial diameter, preferably 1-1.5 times thedeployment diameter of the stent. In a preferred embodiment, the stentis capable of being crimped from an expanded diameter to a crimpeddiameter, and at body temperature is capable to expand from a crimpedconfiguration to a deployed diameter without fracture and havesufficient strength to support a body lumen. Examples of polymericmaterial are materials comprising lactide, lactide and glycolide, orlactides and caprolactones, or a combination thereof.

In some embodiments, the diameter of the tubular body or the polymericmaterial or the stent may, at the time of treatment (e.g., treatmentdiameter), be optionally smaller or optionally greater than thedeployment diameter, where the deployment diameter may include, forexample, the diameter of the tubular body or the stent within a lumen.In some embodiments, the treatment diameter may be 1-2 times thedeployment diameter, or 1-1.9 times the deployment diameter, or 1-1.8times the deployment diameter, or 1-1.7 times the deployment diameter,or 1-1.6 times the deployment diameter, or 1-1.5 times the deploymentdiameter, or 1-1.4 times the deployment diameter, or 1-1.3 times thedeployment diameter, or 1-1.2 times the deployment diameter, or 1-1.05times the deployment diameter. In other embodiments, the treatmentdiameter may be 0.95-1 times the deployment diameter. In otherembodiments, the treatment diameter may be 0.9-1 times the deploymentdiameter, or 0.8-1 times the deployment diameter, or 0.7-1 times thedeployment diameter, or 0.6-1 times the deployment diameter, or 0.5-1times the deployment diameter, or 0.4-1 times the deployment diameter,or 0.3-1 times the deployment diameter, or 0.2-1 times the deploymentdiameter. The stent expanded/deployed diameter typically is 2 mm andhigher, 2.5 mm and higher, 3 mm and higher, 3.5 mm and higher, 4 mm andhigher, 4.5 mm and higher, 5 mm and higher, 5.5 mm and higher. In otherembodiments, the stent deployed diameter ranges from 2 mm-25 mm,preferably ranges from 2.5 mm to 15 mm, more preferably from 3 mm to 10mm. The stent length ranges from 1 mm to 200 cm, preferably from 5 mm to60 cm, more preferably from 5 mm to 6 cm.

In some embodiments, an annealed polymeric article or tube is quenchedby being cooled fast from the annealing temperature to a lowertemperature (e.g., at least about 10° C., 20° C., 30° C., 40° C. or 50°C. below the T_(g), or to ambient temperature or below) over a period ofabout 1 second to about 1 hour, or about 10 seconds to about 1 hour, orabout 30 seconds to about 30 minutes, or about 1 minute to about 30minutes, or about 1 minute to about 15 minutes, or about 1 minute toabout 5 minutes, or about 5 minutes to about 15 minutes, or about 10seconds to about 1 minute. In other embodiments, an annealed article ortube is quenched by being cooled slowly from the annealing temperatureto a lower temperature (e.g., at least about 10° C., 20° C., 30° C., 40°C. or 50° C. below the T_(g), or to ambient temperature or below) over aperiod of about 1 hour to about 24 hours, or about 1 hour to about 12hours, or about 1 hour to about 6 hours, or about 2 hours to about 12hours, or about 4 hours to 12 hours, or about 4 hours to about 8 hours,or about 6 hours to 10 about hours. In some embodiments, a heat-treatedarticle or tube is cooled to a temperature below ambient temperature fora period of about 1 minute to about 96 hours, or about 24 hours to about72 hours, or about 30 minutes to about 48 hours, or about 1 hour toabout 48 hours, or about 1 hour to about 36 hours, or about 1 hour toabout 24 hours, or about 1 hour to about 12 hours, or about 4 hours toabout 12 hours, to stabilize the crystals and/or terminatecrystallization in the polymeric material. Annealing and quenching ofthe polymeric article or tube can initiate and promote nucleation ofcrystals in the polymeric material, increase the mechanical strength ofthe material (e.g., polymeric material) comprising the polymeric articleor tube, and/or reduce residual/internal stress in the polymeric articleor tube. The annealing temperature and duration and the coolingtemperature and rate of cooling can be controlled to optimize the size,number and distribution of the crystals and crystalline regions in thematerial (e.g., polymeric material) and the strength thereof.

In further embodiments, an unannealed or annealed polymeric article ortube is exposed to ionizing radiation (e.g., e-beam or gamma radiation)at, above or below ambient temperature, with a single dose or multipledoses of radiation totaling about 1 kGray (kGy) to about 100 kGy, orabout 10 kGy to about 50 kGy, or about 10 kGy to about 30 kGy, or about20 kGy to about 60 kGy, or about 20 kGy to about 40 kGy. In certainembodiments, an unannealed or annealed article or tube is cooled toreduced temperature (e.g., below 0° C.) and then is exposed to a singledose or multiple doses of ionizing radiation (e.g., e-beam or gammaradiation) totaling about 10 kGy to about 50 kGy.

In a preferred embodiment, there is a desire to minimize the amount ofheat and/or duration the tubular body or the stent or the biodegradablematerial sees after forming. Examples include treating the tubular bodyby heating the tubular body after forming to temperature at about Tg orlower than Tg or within 10° C. higher than Tg, of the biodegradablepolymeric material Tg, for duration ranging from a fraction of a secondto 7 days, or 5 seconds to 7 days, preferably from 15 seconds to 1 day,more preferably from 30 seconds to 5 hours, and optionally cooling orquenching after heating to above ambient, ambient temperatures or belowambient. The heating can take place once or more than once at variousstages of the tubular body or stent prosthesis fabrication. In oneembodiment, the biodegradable stent prosthesis comprising a tubular bodycomprising a biodegradable polymeric material, wherein the tubular bodyhas been formed using extrusion, molding, dipping, or spraying and hasbeen treated by heating the tubular body at about Tg or lower of thebiodegradable polymeric material Tg, said biodegradable polymericmaterial is substantially amorphous after said treatment and has a Tggreater than 37° C., and the stent prosthesis at body temperature isradially expandable and has sufficient strength to support a body lumen.In another embodiment, the biodegradable stent prosthesis comprising atubular body comprising a biodegradable polymeric material, wherein thetubular body has been formed using extrusion, molding, dipping, orspraying and has been treated by heating the tubular body at about Tg orlower of the biodegradable polymeric material Tg, said biodegradablepolymeric material has crystallinity of 10%-60% (or 10%-50% or 10%-40%or 10% to 30% or 10%-20% or 0%-10% or 0% to 30%) after said treatmentand has a Tg greater than 37° C., and the stent prosthesis at bodytemperature is radially expandable and has sufficient strength tosupport a body lumen. In one embodiment, the Tg is greater than 37° C.and less than 60° C., preferably greater than 37° C. and less than 55°C., more preferably greater than 37° C. and less than 45° C., morepreferably greater than 35° C. and less than 45° C.

In another preferred embodiment, there is a desire to minimize theamount of heat and/or duration the tubular body or the stent or thebiodegradable material sees after forming Examples include treating thetubular body by heating the tubular body after forming to temperature atabout Tg or lower than Tg or within 10° C. higher than Tg, or having one(or more than one) heat treatment above Tg, of the biodegradablepolymeric material Tg, for duration ranging from a fraction of a secondto 7 days, preferably from 15 seconds to 1 day, more preferably from 30seconds to 5 hours, and optionally cooling or quenching, after heating,to above ambient, ambient temperatures or below ambient. The heating cantake place once or more than once at various stages of the tubular bodyor stent prosthesis fabrication. In one embodiment, the biodegradablestent prosthesis comprising a tubular body comprising a biodegradablepolymeric material, wherein the tubular body has been formed usingextrusion, molding, dipping, or spraying and has been treated by heatingthe tubular body at about Tg or lower of the biodegradable polymericmaterial Tg and one heat treatment above Tg, said biodegradablepolymeric material is substantially amorphous after said treatments andhas a Tg greater than 37° C., and the stent prosthesis at bodytemperature is radially expandable and has sufficient strength tosupport a body lumen. In another embodiment, the biodegradable stentprosthesis comprising a tubular body comprising a biodegradablepolymeric material, wherein the tubular body has been formed usingextrusion, molding, dipping, or spraying and has been treated by heatingthe tubular body at about Tg or lower of the biodegradable polymericmaterial Tg and one heat treatment above Tg, said biodegradablepolymeric material has crystallinity of 10%-60% (or 10%-50% or 10%-40%or 10% to 30% or 10%-20% or 0%-10% or 0% to 30%) after said treatmentand has a Tg greater than 37° C., and the stent prosthesis at bodytemperature is radially expandable and has sufficient strength tosupport a body lumen. In one embodiment, the Tg is greater than 37° C.and less than 60° C., preferably greater than 37° C. and less than 55°C., more preferably greater than 37° C. and less than 45° C., morepreferably greater than 35° C. and less than 45° C.

In a preferred embodiment, there is a desire to minimize the amount ofheat and/or duration the tubular body or the stent or the biodegradablematerial sees after forming. Examples include treating the tubular bodyby heating the tubular body after forming to temperature at about Tg orlower than Tg or within 10° C. higher than Tg, of the biodegradablepolymeric material Tg, for duration ranging from a fraction of a secondto 7 days, or 5 seconds to 7 days, preferably from 15 seconds to 1 day,more preferably from 30 seconds to 5 hours, and optionally cooling orquenching after heating to above ambient, ambient temperatures or belowambient. The heating can take place once or more than once at variousstages of the tubular body or stent prosthesis fabrication. In oneembodiment, the biodegradable stent prosthesis comprising a tubular bodycomprising a biodegradable polymeric material, wherein the tubular bodyhas been formed using extrusion, molding, dipping, or spraying and hasbeen treated by heating the tubular body at about Tg or lower of thebiodegradable polymeric material Tg, said biodegradable polymericmaterial is substantially amorphous after said treatment and has a Tggreater than 37° C., and the stent prosthesis at body temperature isradially expandable and has sufficient strength to support a body lumen.In another embodiment, the biodegradable stent prosthesis comprising atubular body comprising a biodegradable polymeric material, wherein thetubular body has been formed using extrusion, molding, dipping, orspraying and has been treated by heating the tubular body at about Tg orlower of the biodegradable polymeric material Tg, said biodegradablepolymeric material has crystallinity of 10%-60% (or 10%-50% or 10%-40%or 10% to 30% or 10%-20% or 0%-10% or 0% to 30%) after said treatmentand has a Tg greater than 37° C., and the stent prosthesis at bodytemperature is radially expandable and has sufficient strength tosupport a body lumen. In one embodiment, the Tg is greater than 37° C.and less than 60° C., preferably greater than 37° C. and less than 55°C., more preferably greater than 37° C. and less than 45° C., morepreferably greater than 35° C. and less than 45° C.

In some embodiments, the endoprosthesis (e.g., a stent) or the polymericarticle (e.g., a polymeric tube) from which it is formed, with orwithout at least one surface being positioned against a non-deformablesurface (e.g., the stent or the polymeric tube optionally being placedinside a non-deformable tube having a larger diameter), is pressurizedto at least about 100 psi, 200 psi, 300 psi, 400 psi, 500 psi, 600 psior 700 psi, with or without added heat, and in the presence or absenceof carbon dioxide gas or liquid.

In further embodiments, the material (e.g., polymeric material)comprising the body of an endoprosthesis (e.g., a stent) has increasedstrength and/or crystallinity (e.g., through induced or increasedorientation of crystals, crystalline regions or polymer chains), and/orhas reduced residual or internal stress, by at least heating theendoprosthesis and/or the polymeric article (e.g., a polymeric tube)from which it is formed at a temperature equal to the T_(g), or abovethe T_(g) and below the T_(m), or equal to or above the T_(m), of thematerial (e.g., polymeric material), or below Tg, for a period of time(e.g., at least about 0.01, 1, 4, 8, 12, 24, 36 or 48 hours), andquickly or slowly cooling the endoprosthesis and/or the polymericarticle to a lower temperature (e.g., at least about 10° C., 20° C., 25°C., 30° C., 40° C. or 50° C. below the T_(g), or to ambient temperatureor below); or by at least minimizing heating conditions of the tubularbody or stent during processing such that % crystallinity does notincrease by more than 20% or between 1% to about 20%. In someembodiments, the material (e.g., polymeric material) comprising the bodyof an endoprosthesis (e.g., a stent) has increased strength and/orcrystallinity, and/or has reduced residual or internal stress, byheating the endoprosthesis and/or the polymeric article (e.g., apolymeric tube) from which it is formed at a temperature at least about1° C., 5° C., 10° C., 20° C., 30° C., 40° C. to about 50° C. (e.g.,polymeric material) for a period of time (e.g., at least about 0.1, 4,8, 12, 24, 36 or 48 hours), and quickly or slowly cooling theendoprosthesis and/or the polymeric article to lower temperature (e.g.,at least about 10° C., 20° C., 25° C., 30° C., 40° C. or 50° C. belowthe T_(g), or to ambient temperature or below). In certain embodiments,the endoprosthesis and/or the polymeric article are heated at atemperature equal to or no more than about 1° C., 5° C., 10° C., 15° C.,20° C., 25° C. or 30° C. below the temperature used to induce orincrease orientation of crystals, crystalline regions or polymer chainsof the material (e.g., polymeric material) comprising the endoprosthesisor the polymeric article.

Another modification treatment that a polymeric article (e.g., apolymeric tube) and/or an endoprosthesis (e.g., a stent) can undergo iscrosslinking. A polymeric material comprising the body of theendoprosthesis and/or a polymeric material comprising any coating on theendoprosthesis can be crosslinked by exposure to radiation (e.g., UVradiation or ionizing radiation, such as e-beam or gamma radiation),exposure to heat, use of a crosslinker, or use of a crosslinking agentand an initiator, as described herein. In certain embodiments, thepolymeric material(s) are crosslinked by exposure to e-beam or gammaradiation having a cumulative dose of about 1 kGy to about 1000 KGy, orabout 5 kGy to about 100 kGy, or about 10 kGy to about 50 kGy, or about10 kGy to about 30 kGy, or about 20 kGy to about 60 kGy, or about 20 kGyto about 40 kGy. Crosslinking of the polymeric material(s) can beperformed, e.g., to increase their crystallinity and/or reduce recoil ofan endoprosthesis (e.g., a stent) comprised of the polymericmaterial(s).

In another embodiment, the biodegradable stent material has increasedcrystallinity by increasing orientation of polymer chains with in thebiodegradable stent material in radial and/or longitudinal direction bydrawing, pressurizing and/or heating the stent material. In anotherembodiment, the drawing, pressurizing and/or heating the stent materialoccurs simultaneously or sequentially.

In one embodiment, the biodegradable stent material is placed with atleast one surface against a non deformable surface and is pressurized toat least 200 psi, preferably to at least 300 psi, more preferably to atleast 500 psi. In another embodiment, the biodegradable stent materialis pressurized to at least 200 psi, preferably to at least 300 psi, morepreferably to at least 500 psi.

In one embodiment, the biodegradable stent material tube is placed within a larger diameter non deformable tube and is pressurized to at least200 psi, preferably to at least 300 psi, more preferably to at least 500psi. In another embodiment, the biodegradable stent material tube ispressurized to at least 200 psi, preferably to at least 300 psi, morepreferably to at least 500 psi.

In one embodiment, the biodegradable stent material has increasedcrystallinity by increasing the orientation of the polymer chains by atleast heating the biodegradable stent material above its glasstransition temperature (Tg) and below its melting temperature.

In one embodiment, the biodegradable stent material has increasedcrystallinity by heating the material to a temperature at least 10° C.higher than its Tg, preferably at least 20° C. higher, more preferablyat least 30° C. higher than the Tg of the biodegradable stent material.

In one embodiment, biodegradable stent material has increasedcrystallinity after drawing, heat and/or pressurizing and annealing atelevated temperature with or without vacuum. In one embodiment, theannealing temperature is below the temperature used for orientation ofthe polymer chains of the biodegradable stent material. In anotherembodiment, the annealing temperature is at most 20° C. below,preferably at most 15° C. below, more preferably at most 10° C. belowthe temperature for orientation of the polymer chains of thebiodegradable stent material.

In one embodiment, the biodegradable stent material after annealing isquenched below Tg of the biodegradable stent material, preferably atleast 25° C. below Tg, more preferably at least 50° C. below Tg of thebiodegradable stent material.

The polymeric material or the tubular body formed there from can bemodified to control crystallinity (e.g., degree of crystallinity) of thepolymeric material. In certain embodiments, the substantially amorphousor semi-crystalline polymeric material or the tubular body formedtherefrom undergoes a modification treatment to introduce a desireddegree of crystallinity into the polymeric material to increase thestrength of the polymeric material without substantially lengthening itsdegradation time. In another embodiment, tubular body comprising thepolymer or copolymer comprised of at least one of PLLA, PLLA-PCL, orPLGA, wherein the tubular body or stent is substantially amorphous orsemi crystalline after modification. In another embodiment, the tubularbody comprising the polymer or copolymer is comprised of at least one ofPLLA, PLLA-PCL, or PLGA, wherein the tubular body or stent issubstantially amorphous or semi crystalline after modification, andwherein the crystallinity ranges from about 5% to about 40%. In anotherembodiment, the tubular body comprising the polymer or copolymer iscomprised of at least one of PLLA, PLLA-PCL, PLGA, wherein the tubularbody or stent is substantially amorphous or semi crystalline aftermodification, and wherein the crystallinity ranges from about 5% toabout 30%. In another embodiment, the tubular body comprising thepolymer or copolymer is comprised of at least one of PLLA, PLLA-PCL,PLGA, wherein the tubular body or stent is substantially amorphous orsemi crystalline after modification and wherein the crystallinity rangesfrom about 5% to about 25%.

The treated stent or other endoprosthesis can be crimped onto a deliveryballoon using mechanical crimpers comprising of wedges such as crimpersfrom Machine Solutions, Fortimedix, or others. The stent can also becrimped by placing the stent in a shrink tube and stretching the shrinktube slowly at a rate of 0.1 to 2 inches/minutes, more preferably 0.2 to0.5 inches/minutes until the stent is crimped to the desired crimpeddiameter. During crimping, the stent is heated to a temperature of 20°C. below the Tg to 10° C. above the Tg for 30 minutes, more preferablyto 10° C. below the Tg to Tg, and most preferably at the Tg of the stentmaterial. This process facilitates or enables the stent to maintain thefinal crimped diameter. After crimping, the ability for the stent toremain the crimped diameter can further be improved by fixing the stentin the crimped diameter while exposing it to a temperature of 20° C.below the Tg to 10° C. above the Tg for 30 minutes, more preferably to10° C. below the Tg to Tg, and most preferably at the Tg of the stentmaterial, for 1 minute to 24 hours, more preferably 15 minutes to 1hour. After holding at this crimping temperature, it is preferred to fixthe stent in the crimped diameter while at or below ambient temperaturesuntil further processing (i.e., sterilization). The stent can either becrimped while it is on the balloon of the stent delivery catheter orfirst crimped alone and then slipped onto the balloon of the catheter.In a further embodiment, the crimped stent is cooled below ambienttemperature to lock in the crystals or terminate crystallization for 1minute to 96 hours, more preferably 24 hours to 72 hours.

In a preferred embodiment, the final crimped stent on the catheter issterilized by 25 to 30 kGy dose of ebeam, typically with a single doseof 30 kGy or with multiple smaller doses (e.g., 3×10 kGy). The stentsystem is usually kept below ambient temperature before, during and/orafter multiple smaller doses of sterilization. The stent that has beenpackaged and sterilized can also be exposed to heat treatment like thatdescribed above. In one embodiment, the biodegradable polymer stent isheated at about the Tg of the biodegradable stent material duringexpansion of the stent. The temperature during expansion can range from10° C. above Tg to 10° C. below Tg.

Upon deployment of such stent, the processes provide means to minimizestent recoil to less than 10% after expansion from the crimped state toan expanded state.

A stent can be crimped to a smaller diameter using a mechanical crimper.A stent can also be crimped by placing the stent in a shrink tube andstretching the shrink tube slowly at a rate of about 0.1 to about 2inches/minute, or about 0.1 to about 1 inch/minute, or about 0.2 toabout 0.5 inch/minute, until the stent is crimped to the desireddiameter. A stent can be crimped onto the balloon of a deliverycatheter, or can be crimped and then mounted onto the balloon of acatheter to provide a stent delivery system.

In certain embodiments, a stent is crimped at ambient temperature, or iscrimped at a temperature (crimping temperature) of at least about 30°C., 35° C., 40° C., 45° C. or 50° C., and then the stent crimped atelevated temperature is cooled to a lower temperature (e.g., at leastabout 5° C., 10° C., 15° C., 20° C., 25° C. or 30° C. below the crimpingtemperature, or to ambient temperature or below). In an embodiment, thestent is crimped at about 35° C. or above, and then the crimped stent iscooled to a temperature at least about 5° C. below the crimpingtemperature. In further embodiments, the crimping temperature is at orbelow the T_(g) of the material (e.g., polymeric material) of which thestent body is composed, or at least about 1° C., 5° C., 10° C., 15° C.,20° C., 25° C., 30° C., 35° C., 40° C., 45° C. or 50° C. below theT_(g). In an embodiment, the crimping temperature is at least about 5°C. below the T_(g) of the material (e.g., polymeric material) comprisingthe stent body.

In some embodiments, a stent is exposed to the crimping temperature forat least about 0.5, 1, 3, 5 or 10 minutes and allowed to reach thecrimping temperature prior to being crimped. The stent can be exposed tothe crimping temperature using a heated crimper. The crimped stent canbe stabilized in the crimped state as described herein. In additionalembodiments, the crimped stent is cooled below ambient temperature for aperiod of about 1 minute to about 96 hours, or about 24 hours to about72 hours, or about 30 minutes to about 48 hours, or about 1 hour toabout 48 hours, or about 1 hour to about 36 hours, or about 1 hour toabout 24 hours, or about 1 hour to about 12 hours, or about 4 hours toabout 12 hours, to stabilize the stent, and/or stabilize the crystalsand/or terminate crystallization in the stent polymeric material.

In some embodiments, a stent is exposed to carbon dioxide gas atelevated pressure (e.g., at least about 100, 150, 200, 250, 300, 350,400, 450 or 500 psi) for a period of time (e.g., at least about 10, 20or 30 minutes, or at least about 1, 2 or 3 hours), e.g., to soften thematerial (e.g., polymeric material) comprising the body of the stentand/or a coating on the stent. After exposure to carbon dioxide, thestent can be crimped at or below the T_(g) of the material (e.g.,polymeric material) comprising the body of the stent (e.g., at leastabout 1° C., 5° C., 10° C., 15° C., 20° C., 25° C., 30° C., 35° C., 40°C., 45° C. or 50° C. below the T_(g)), or at about ambient temperatureto about 50° C.

An endoprosthesis (e.g., a stent or a stent delivery system) and/or thepolymeric article (e.g., a polymeric tube) from which it is formed canbe exposed to ionizing radiation such as electron beam or gammaradiation or to ethylene oxide gas (e.g., for purposes of sterilization)as described herein. In addition to serving as a sterilizationtreatment, such exposure can serve as a modification or treatment inthat it can, e.g., control crystallinity (e.g., degree of crystallinity)and/or enhance the strength of the material (e.g., polymeric material)comprising the polymeric article or the endoprosthesis. In someembodiments, the polymeric article and/or the endoprosthesis are exposedto a single dose or multiple doses of e-beam or gamma radiation totalingabout 5 or 10 kGy to about 50 kGy, or about 20 kGy to about 40 kGy ofradiation, e.g., a single dose of 30 kGy or multiple smaller doses(e.g., 3×10 kGy doses), where the polymeric article and/or theendoprosthesis are cooled to low temperature (e.g., about −10° C. toabout −30° C., or about −20° C.) for a period of time (e.g., at leastabout 20, 30 or 40 minutes) prior to exposure to the single dose or toeach of the multiple doses of radiation. In certain embodiments, thepolymeric article and/or the endoprosthesis are exposed to a single doseor multiple doses of e-beam or gamma radiation totaling about 10 kGy toabout 50 kGy, or about 30 kGy. A polymeric article and/or anendoprosthesis that have been exposed to ionizing radiation or ethyleneoxide gas can also undergo one or more other modification treatments(e.g., heating or annealing) described herein.

In certain embodiments, an endoprosthesis (e.g., a stent) is patternedby laser cutting or other method from a polymeric tube that has a (e.g.,inner or outer) diameter substantially equal to or smaller than anintended deployed (e.g., inner or outer) diameter of the endoprosthesis.In other embodiments, an endoprosthesis (e.g., a stent) is patternedfrom a polymeric tube that has a (e.g., inner or outer) diameter, eitherwhen the tube is formed or after the tube is radially expanded to asecond larger diameter, larger than an intended deployed (e.g., inner orouter) diameter of the endoprosthesis. Patterning a stent from apolymeric tube having a (e.g., inner or outer) diameter larger than anintended deployed (e.g., inner or outer) diameter of the stent canimpart advantageous characteristics to the stent, such as reducingradially inward recoil of the stent after deployment. In certainembodiments, a stent is patterned from a polymeric tube having a (e.g.,inner or outer) diameter about 0.85, 0.90, 1.0, 1.05 to about 1.5 times,or about 1.1 to about 1.5 times, or about 1.1 to about 1.3 times, orabout 1.15 to about 1.25 times, smaller, same, or larger than anintended deployed (e.g., inner or outer) diameter of the stent. In anembodiment, the stent is patterned from a polymeric tube having a (e.g.,inner or outer) diameter about 1.1 to about 1.3 times larger than anintended deployed (e.g., inner) diameter of the stent. For example, astent having a deployed (e.g., inner or outer) diameter of about 2.5, 3or 3.5 mm can be patterned from a tube having a (e.g., inner or outer)diameter of about 2.75, 3.3 or 3.85 mm (1.1 times larger), or about3.25, 3.9 or 4.55 mm (1.3 times larger), or some other (e.g., inner orouter) diameter larger than the deployed (e.g., inner or outer) diameterof the stent. In other embodiments, the initial diameter of the formedtube is larger than the crimped diameter (e.g., crimped diameter on adelivery system) of the stent prosthesis wherein the tubular body isexpanded to a second larger diameter than the initial diameter beforepatterning or before crimping to the crimped diameter; or wherein thetubular body remains substantially the same diameter before patterningor before crimping to a crimped diameter; or wherein the tubular body iscrimped to a smaller diameter than the initial formed diameter beforepatterning or after patterning. In another embodiment, the initialdiameter of the formed tube is smaller than the crimped diameter of thestent prosthesis wherein the tubular body is expanded to a second largerdiameter than the initial diameter before patterning or before crimping;or wherein the tubular body remains substantially the same diameterbefore patterning or before crimping; or wherein the tubular body iscrimped to a smaller diameter than the crimped diameter of the stentprosthesis before patterning or after patterning. In another embodiment,the initial diameter of the formed tubular body is greater than 0.015inches, or greater than 0.050 inches, or greater than 0.092 inches, orgreater than 0.120 inches, or greater than 0.150 inches. Stentprosthesis intended deployment diameter is the diameter of the labeleddelivery system or balloon catheter. For example when a stent prosthesisis crimped onto a balloon labeled 3.0 mm diameter, the stent prosthesis'intended deployment diameter is 3.0 mm. Similarly, self expandable stentcrimped onto a delivery system is labeled a certain deployment diameter.

The stent cut from a polymeric tube can be any kind of stent and canhave any pattern and design suitable for its intended use, including anykind of stent and any pattern and design described herein. Further, thestent can be a fully self-expandable stent, a balloon-expandable stent,or a stent capable of radially self-expanding prior to balloon expansionto an intended deployed diameter.

The stent material may lose some crystallinity during stent cutting. Insuch cases, the stent annealed after cutting and/or a second time tore-crystallize the polymer to a higher crystallinity. Thus, the cutstent may be annealed a second time as generally described above.Annealing/heating followed by cooling as described above can be repeatedone or more times to further increase crystallinity. In a furtherembodiment, the heat treated stent is cooled below ambient temperatureto lock in the crystals or terminate crystallization for 1 minute to 96hours, more preferably 24 hours to 72 hours.

In certain embodiments, the polymeric article is a polymeric tube andthe structure is a substantially cylindrical structure. In anembodiment, the substantially cylindrical structure is a mandrel.

In further embodiments, the polymeric tube is substantially concentric.In certain embodiments, the polymeric tube has a concentricity of about0.0025 inch (about 64 microns) or less, or about 0.002 inch (about 51microns) or less, or about 0.0015 inch (about 38 microns) or less, orabout 0.001 inch (about 25 microns) or less, or about 0.0005 inch (about13 microns) or less, or about 0.00025 inch (about 6 microns) or less. Inan embodiment, concentricity is two times the distance between thecenters of the inner and outer diameters of the tube. In someembodiments, the polymeric tube has a percent concentricity of at leastabout 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%.In an embodiment, percent concentricity is calculated as follows: %concentricity=(minimum wall thickness/maximum wall thickness)×100. Incertain embodiments, the polymeric tube has a concentricity of about0.001 inch (about 25 microns) or less, or a percent concentricity of atleast about 90%.

When the biodegradable device is a stent, in some embodiments the stentis patterned from a polymeric tube that has a (e.g., inner) diametersubstantially equal to an intended deployment (e.g., inner) diameter orthe maximum allowable expansion (e.g., inner) diameter of the stent. Inother embodiments, the stent is patterned from a polymeric tube that hasa (e.g., inner) diameter greater than (e.g., at least about 5%, 10%,15%, 20%, 25%, 30%, 35%, 40%, 45% or 50% greater than) an intendeddeployment (e.g., inner) diameter or the maximum allowable expansion(e.g., inner) diameter of the stent. In an embodiment, the stent ispatterned from a polymeric tube that has a (e.g., inner) diameter atleast about 10% greater than an intended deployment (e.g., inner)diameter or the maximum allowable expansion (e.g., inner) diameter ofthe stent. In some embodiments, the stent is patterned from a polymerictube that has a (e.g., inner) diameter of about 2.5 mm to about 4.5 mm,or about 2.75 mm to about 4.5 mm, or about 3 mm to about 4.5 mm, orabout 2.75 mm to about 4 mm, or about 3 mm to about 4 mm, or about 3.3mm to about 3.8 mm. In certain embodiments, the stent is patterned froma polymeric tube that has a (e.g., inner) diameter of about 2.75 mm toabout 4.5 mm, or about 2.75 mm to about 4 mm.

In one embodiment, the tubular body or stent prosthesis diameter rangesfrom about 0.25 mm to about 25 mm, preferably from about 2 mm to about15 mm, more preferably from about 2.5 mm to about 10 mm, and mostpreferably from about 3 mm to about 7 mm.

The stent or other endoprosthesis is patterned from a tube of the stentmaterial in an expanded diameter and subsequently crimped to a smallerdiameter and fitted onto a balloon of a delivery catheter. The stent ispatterned, typically by laser cutting, with the tubing diameter about 1to 1.3 times, preferably 1.1 to 1.5 times, more preferably 1.15 to 1.25times, larger the intended deployed diameter. For example, a stent cutat a 3.5 mm×18 mm outer diameter is crimped on a 3.0 mm×18 mm stentdelivery catheter. In a further embodiment, the unannealed and/orannealed stent is exposed to ebeam or gamma radiation, with single ormultiple doses of radiation ranging from 5 kGy to 100 kGy, morepreferably from 10 kGy to 50 kGy.

An intended deployment diameter is one or more of the following: thelabeled deployment diameter of the stent prosthesis. An example is astent prosthesis IFU or box or label with a certain labeled diametersuch as a nominal deployment diameter, for example 3.0 mm. It can alsobe the deployed diameter of the stent prosthesis. It can also be adiameter between a nominal deployment diameter and the rated burstdiameter or higher. It can also be the diameter (where in the case of aballoon or mechanical expansion) where the balloon is expanded to atleast 90% of the nominal diameter of the balloon. The most preferredembodiment of an intended deployment diameter is the labeled deploymentdiameter or the nominal deployment diameter.

In a preferred embodiment, when the stent is expanded to at least 1times or at least 1.1 times or at least 1.15 times or at least 1.2 timesor at least 1.25 time or at least 1.3 times, or at least 1.4, or atleast 1.5 times deployed diameter or an intended deployment diameter at37° C., wherein the stent prosthesis is capable of expansion to at leastsaid diameters without breakage/fracture in one or more of the stentprosthesis struts, crowns, or links.

In another embodiment, when the stent is expanded to at least 1 times orat least 1.1 times or at least 1.15 times or at least 1.2 times or atleast 1.25 time or at least 1.3 times a deployed diameter or an intendeddeployment diameter in a body lumen or in water at 37° C., wherein thestent prosthesis is capable of expansion to at least said diameterswithout breakage/fracture in two or more of the stent prosthesis struts,crowns, or links.

In one embodiment, when the stent is expanded to at least 1 times or atleast 1.1 times or at least 1.15 times or at least 1.2 times or at least1.25 time or at least 1.3 times an intended deployment diameter in abody lumen or in water at 37° C., wherein the stent prosthesis iscapable of expansion to at least said diameters withoutbreakage/fracture in three or more of the stent prosthesis struts,crowns, or links.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga biodegradable polymeric material, wherein the polymeric material hasbeen formed using extrusion, molding, dipping, 3D printing, or spraying,said biodegradable polymeric material has been treated at a diameter of1-1.5 times an intended deployment diameter (deployed diameter) of thestent prosthesis, and the stent prosthesis at body temperature isradially expandable and has sufficient strength to support a body lumenand without fracture.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga biodegradable polymeric material, wherein the polymeric material hasbeen formed using extrusion, molding, dipping, 3D printing, or spraying,said biodegradable polymeric material has been treated at a diameter of1-1.5 times an intended deployment diameter (deployed diameter) of thestent prosthesis, wherein the treatment comprises heating the polymericmaterial to between Tg and Tm (melting temperature of the material), andthe stent prosthesis at body temperature is radially expandable and hassufficient strength to support a body lumen and without fracture.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga biodegradable polymeric material, wherein the polymeric material hasbeen formed using extrusion, molding, dipping, 3D printing, or spraying,said biodegradable polymeric material has been treated at a diameter of1-1.5 times an intended deployment diameter of the stent prosthesis,wherein the treatment comprises heating the polymeric material to aboutTg or less, and the stent prosthesis at body temperature is radiallyexpandable and has sufficient strength to support a body lumen andwithout fracture.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga biodegradable polymeric material, wherein the polymeric material hasbeen formed using extrusion, molding, dipping, 3D printing, or spraying,said biodegradable polymeric material has been treated at a diameter of1-1.5 times an intended deployment diameter of the stent prosthesis,wherein the treatment comprises heating the polymeric material to aboutTg or less or/and about Tg or more from at least a fraction of a secondto about 7 days, and the stent prosthesis at body temperature isradially expandable and has sufficient strength to support a body lumenand without fracture.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated at a diameter of 1-1.5 times an intended deployment diameter ofthe stent prosthesis, wherein the treatment comprises heating thepolymeric material from about Tg or higher, and the stent prosthesis atbody temperature is radially expandable and has sufficient strength tosupport a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisingbiodegradable polymeric material, wherein the polymeric material hasbeen formed using extrusion, molding, dipping, 3D printing, or spraying,said biodegradable polymeric material has been treated at a diameter of1-1.5 times an intended deployment diameter of the stent prosthesis,wherein the treatment comprises heating the polymeric material fromabout Tg or higher and wherein the polymeric material has crystallinityafter treatment between 0% to 60%, and the stent prosthesis at bodytemperature is radially expandable and has sufficient strength tosupport a body lumen and without fracture.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga biodegradable polymeric material, wherein the polymeric material hasbeen formed using extrusion, molding, dipping, 3D printing, or spraying,said biodegradable polymeric material has been treated at a diameter of1-1.5 times an intended deployment diameter of the stent prosthesis,wherein the treatment comprises heating the polymeric material fromabout Tg or higher and wherein the polymeric material has crystallinityafter treatment between 0% to 60%, and the stent prosthesis at bodytemperature is radially expandable and has sufficient strength tosupport a body lumen and without fracture.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated at a diameter of 0.75-1.5 times an intended deployment diameterof the stent prosthesis, wherein the treatment comprises heating thepolymeric material from about Tg or less to about Tg or higher andwherein the polymeric material has crystallinity after treatment between0% to 60%, and the stent prosthesis at body temperature is radiallyexpandable and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated at a diameter of 0.85-1.5 times an intended deployment diameterof the stent prosthesis, wherein the treatment comprises heating thepolymeric material from about Tg or less to about Tg or higher andwherein the polymeric material has crystallinity after treatment between0% to 60%, and the stent prosthesis at body temperature is radiallyexpandable and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated at a diameter of 0.9-1.5 times an intended deployment diameterof the stent prosthesis, wherein the treatment comprises heating thepolymeric material from about Tg or less to about Tg or higher andwherein the polymeric material has crystallinity after treatment between0% to 60%, and the stent prosthesis at body temperature is radiallyexpandable and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated at a diameter of 0.75-1.5 times an intended deployment diameterof the stent prosthesis, wherein the treatment comprises heating thepolymeric material from about Tg or less to about Tg or higher andwherein the polymeric material has crystallinity after treatment between0% to 60%, and the stent prosthesis is radially expandable to anintended deployment diameter at a temperature ranging from greater than37° C. to 50° C. and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated at a diameter of 0.75-1.5 times an intended deployment diameterof the stent prosthesis, wherein the treatment comprises heating thepolymeric material from about Tg or less to about Tg or higher andwherein the polymeric material has crystallinity after treatment between0% to 60%, and the stent prosthesis at body temperature is radiallyexpandable to an intended deployment diameter and has sufficientstrength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated at a diameter of 0.75-1.5 times an intended deployment diameterof the stent prosthesis, wherein the treatment comprises heating thepolymeric material from about Tg or less to about Tg or higher andwherein the polymeric material has crystallinity after treatment between0% to 60%, and the stent prosthesis at body temperature is radiallyexpandable to at least 1.0 times an intended deployment diameter and hassufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated at a diameter of 0.75-1.5 times an intended deployment diameterof the stent prosthesis, wherein the treatment comprises heating thepolymeric material from about Tg or less to about Tg or higher andwherein the polymeric material has crystallinity after treatment between0% to 60%, and the stent prosthesis at body temperature is radiallyexpandable to at least 1.1 times an intended deployment diameter and hassufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated at a diameter of 0.75-1.5 times an intended deployment diameterof the stent prosthesis, wherein the treatment comprises heating thepolymeric material from about Tg or less to about Tg or higher andwherein the polymeric material has crystallinity after treatment between0% to 60%, and the stent prosthesis at body temperature is radiallyexpandable to at least 1.15 times an intended deployment diameter andhas sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated at a diameter of 0.75-1.5 times an intended deployment diameterof the stent prosthesis, wherein the treatment comprises heating thepolymeric material from about Tg or less to about Tg or higher andwherein the polymeric material has crystallinity after treatment between0% to 60%, and the stent prosthesis at body temperature is radiallyexpandable to at least 1.2 times an intended deployment diameter and hassufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated at a diameter of 0.75-1.5 times an intended deployment diameterof the stent prosthesis, wherein the treatment comprises heating thepolymeric material from about Tg or less to about Tg or higher andwherein the polymeric material has crystallinity after treatment between0% to 60%, and the stent prosthesis is radially expandable to anintended deployment diameter at a temperature ranging from 30° C. toless than 37° C. and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.0 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.1 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.11 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.12 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.13 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.14 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.15 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.16 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.17 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.18 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.18 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.19 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.2 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.21 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.22 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.23 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.24 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.25 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.26 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.27 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.28 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.29 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable toat least 1.3 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated and said polymeric material has crystallinity between 0% to 60%,and the stent prosthesis at body temperature is radially expandable togreater than 1.1 times an intended deployment diameter of the stentprosthesis and has sufficient strength to support a body lumen and hasrecoil of less than 10% from an expanded diameter.

In a preferred embodiment, the biodegradable stent prosthesis comprisinga tubular body comprising a biodegradable polymeric material, whereinthe tubular body has been formed using extrusion, molding, dipping, 3Dprinting, or spraying, said biodegradable polymeric material has beentreated at a diameter of 0.9-1.5 times an intended deployment diameterand said polymeric material after treatment has crystallinity between 0%to 60% and Tg between 37° C. and 50° C., and the stent prosthesis atbody temperature is radially expandable to greater than 1.1 times anintended deployment diameter of the stent prosthesis and has sufficientstrength to support a body lumen and has recoil of less than 10% from anexpanded diameter.

In another embodiment, the tubular body is formed at a diameter of 0.75to 1.5 times an intended deployment diameter of the stent prosthesis. Inyet another embodiment, the tubular body is formed at a diameter lessthan an intended deployment diameter and expanded to a diameter of 0.75to 1.5 times an intended deployment diameter before patterning or beforecrimping the stent prosthesis. In a further embodiment, the tubular bodyis formed at a diameter less than an intended deployment diameter.

Yet further embodiments of the disclosure relate to a biodegradablestent comprising a body comprising or comprised of a material whichcomprises a biodegradable polymer or copolymer or polymer blend, whereinprior to being balloon-expanded, the stent is capable of radiallyself-expanding by about 0.025 inch (about 635 microns) or less, or byabout 25% or less of an initial crimped diameter of the stent, afterbeing in aqueous condition at about 37° C. in vitro or in vivo for about5 minutes or less. In some embodiments, prior to being balloon-expanded,the stent radially self-expands by about 0.025 inch (about 635 microns)or less, or by about 25% or less of the initial crimped diameter of thestent, after being in aqueous condition at about 37° C. in vitro or invivo for about 5 minutes or less.

Yet further embodiments of the disclosure relate to a biodegradablestent comprising a body which comprises a biodegradable polymer orcopolymer, wherein prior to being balloon-expanded, the stent is capableof radially self-expanding by about 0.001-0.025 inches, or about0.003-0.015 inches, or about 0.005-0.10 inches, or about 0.001 inches ormore, or about 0.003 inches or more, or about 0.005 inches or more, orabout 0.010 inches or more, or about 0.025 inch or more, or by about0.25% or more of an initial crimped diameter of the stent, after beingin aqueous condition at about 37° C. in vitro or in vivo for about 1minute or less, or about 5 minutes or less, or about 15 minutes or less.In some embodiments, prior to being balloon-expanded, the stent radiallyself-expands by about 0.025 inch or less, or by about 25% or less of thecrimped diameter of the stent, after being in aqueous condition at about37° C. in vitro or in vivo for about 1 minute or less, or about 5minutes or less, or about 15 minutes or less. In some embodiments, thestent is secured in place at least in part from moving at least in onelongitudinal direction by about 0.5 mm or less, or about 1 mm or less,or about 2 mm or less, or about 5 mm or less, by various means. Suchmeans include at least one of configuring an expandable member proximaland/or distal to the stent, configuring a non expandable member or stopsproximal and/or distal to the stent, configuring an attachment oradhesive means adjacent to the stent that does not prevent the stentfrom being balloon expandable, or configuring a sleeve that endsproximal to the stent, on top of the sent or distal to the stent.

In a further embodiment, the biodegradable stent comprising a body whichcomprises a biodegradable polymer, or copolymer, polymer blends, polymerblocks, polymer mixture wherein the polymer material is configured to becapable of being balloon expandable and self expanding, wherein prior tobeing balloon-expanded, the stent self-expands by about 0.001-0.025inches, or about 0.003-0.015 inches, or about 0.005-0.10 inches, orabout 0.001 inches or more, or 0.003 inches or more, or 0.005 inches ormore, or 0.010 inches or more, or 0.025 inch or more, or by about 0.25%or more of an initial crimped diameter of the stent, after being inaqueous condition at about 37° C. in vitro or in vivo for about 1minute, or about 5 minutes or less, or about 15 minutes or less.

In a further embodiment, the biodegradable stent comprising a body whichcomprises a biodegradable copolymer or polymer, or mixture of 2-3polymers, or blend of polymers, or wherein the copolymer or polymer isconfigured to be capable of balloon expandable and self expanding,wherein prior to being balloon-expanded, the stent radially self-expandsby about 0.001-0.025 inches, or about 0.003-0.015 inches, or 0.005-0.10inches, or about 0.001 inches or more, or about 0.003 inches or more, orabout 0.005 inches or more, or about 0.010 inches or more, or about0.025 inch or more, or by about 0.25% or more of an initial crimpeddiameter of the stent, after being in aqueous condition at about 37° C.in vitro or in vivo for about 1 minute or less, or about 5 minutes orless, or about 15 minutes or less, and wherein the stent or the stentbody has one or more of the following properties: radial strength ofabout 5 psi to about 20 psi, or about 5 psi or greater, or about 10 psior greater, or about 15 psi or greater, recoil of about 3%-10% or about10% or less, or % elongation at break >50%, or about 100%-about 600%, orabout 50% to about 300%, or Tg of about 37° C.-60° C. or Tg of about 45°C.-55° C., after being in aqueous condition at about 37° C. in vitro orin vivo for about 1 minute or less, or about 5 minutes or less, or about15 minutes or less.

In a further embodiment, the biodegradable stent comprising a body whichcomprises a biodegradable copolymer or polymer, wherein the copolymer orpolymer is configured to be balloon expandable and self expanding,wherein prior to being balloon-expanded, the stent radially self-expandsby about 0.025-0.25 inches, or about 0.50-0.15 inches, or about 0.025inches or more, or about 0.050 inches or more, or about 0.1 inches ormore, or by about 0.25% or more of an initial crimped diameter of thestent, after being in aqueous condition at about 37° C. in vitro or invivo for about 1 minute or less, or about 5 minutes or less, or about 15minutes or less. Optionally, the stent is constrained from selfexpanding using a sheath or other means and then such constraining meansis removed, disengaged, or withdrawn, or released after the stent ispositioned for deployment, allowing the stent to self deploy.

In a further embodiment, the biodegradable stent comprising a body whichcomprises a biodegradable copolymer or polymer, wherein the copolymer orpolymer is configured to be self expanding, wherein prior to beingballoon-expanded, the stent radially self-expanded by about 0.025-0.25inches, or about 0.50-0.15 inches, or about 0.025 inches or more, orabout 0.050 inches or more, or about 0.1 inches or more, or about 0.2inches or more, or by about 0.25% or more of an initial crimped diameterof the stent, after being in aqueous condition at about 37° C. in vitroor in vivo for about 1 minute or less, or about 5 minutes or less, orabout 15 minutes or less. The stent can/may be constrained from selfexpanding using a sheath or other means until the stent is positionedfor deployment and is released from such means for deployment.

In further embodiments, the stent self expands to a diameter that isless than the final intended deployment diameter of the stent prior tobeing balloon expanded to the final intended deployment diameter afterbeing in aqueous condition at about 37° C. in vitro or in vivo for about1 minute or less, or about 5 minutes or less, or about 15 minutes orless.

In some embodiments, the biodegradable stent is a partially or fullyself-expandable stent. In other embodiments, the stent is aballoon-expandable stent. In yet other embodiments, the stent is capableof radially self-expanding initially without a balloon assistingexpansion and is then radially expanded to an intended deploymentdiameter with balloon assistance. In addition, in some embodiments, theimplantable device, prosthesis, and/or articles are configured foruniform expansion (uniformly expanded) during or after either types ofexpansion from a crimped condition to an expanded condition. In someembodiments the stent prosthesis is substantially uniformly expandedfrom a crimped condition. In some embodiments, the stent prosthesis isuniformly expanded from a crimped state to an expanded state wherein thestruts remain intact (or wherein the struts are not broken) afterexpansion from the crimped state. In other embodiments, the stentprosthesis is uniformly expanded at an intended deployment diameterwherein 70% or more of the crowns connecting two struts expand (or open)at an angle (between the struts connected by the crown excluding a linkif present) greater than 75 degrees. In other embodiments, the stentprosthesis is uniformly expanded at an intended deployment diameterwherein 70% or more of the crowns connecting two struts expand (or open)at an angle (between the struts connected by the crown excluding a linkif present) greater than 90 degrees. In other embodiments, the stentprosthesis is uniformly expanded at an intended deployment diameterwherein 70% or more of the crowns connecting two struts expand (or open)at an angle (between the struts connected by the crown excluding a linkif present) greater than 100 degrees. In other embodiments, the stentprosthesis is uniformly expanded at an intended deployment diameterwherein 70% or more of the crowns connecting two struts expand (or open)at an angle (between the struts connected by the crown excluding a linkif present) greater than 120 degrees. In other embodiments, the stentprosthesis is uniformly expanded at an intended deployment diameterwherein 60% or more of the crowns connecting two struts expand (or open)at an angle (between the struts connected by the crown excluding a linkif present) greater than 75 degrees or greater than 90 degrees orgreater than 120 degrees. In some cases a link that joins adjacent ringsis connected to crowns. In such cases, these links are not consideredstruts but are links connecting adjacent rings. Angles for such crownsexclude the presence of links.

In certain embodiments, prior to being balloon-expanded (e.g., to anintended deployment diameter), the biodegradable stent is capable ofradially self-expanding, or radially self-expands, by about 0.015 inch(about 381 microns) or less, or by about 0.01 inch (about 254 microns)or less, or by about 0.007 inch (about 178 microns) or less, or by about0.005 inch (about 127 microns) or less, after being in aqueous condition(e.g., in aqueous solution, water, saline solution or physiologicalconditions) at about 37° C. in vitro or in vivo for about 3 minutes orless, or by about 0.025 inch (about 635 microns) or less, or by about0.02 inch (about 508 microns) or less, or by about 0.015 inch (about 381microns) or less, or by about 0.01 inch (about 254 microns) or less,after being in aqueous condition (e.g., in aqueous solution, water,saline solution or physiological conditions) at about 37° C. in vitro orin vivo for about 5 minutes or less.

In some embodiments, prior to being balloon-expanded (e.g., to anintended deployment diameter), the stent is capable of radiallyself-expanding, or radially self-expands, by about 15% or less, or byabout 10% or less, or by about 5% or less, of the initial crimpeddiameter of the stent after being in aqueous condition (e.g., in aqueoussolution, water, saline solution or physiological conditions) at about37° C. in vitro or in vivo for about 3 minutes or less, or by about 25%or less, or by about 20% or less, or by about 15% or less, or by about10% or less, of the initial crimped diameter after being in aqueouscondition (e.g., in aqueous solution, water, saline solution orphysiological conditions) at about 37° C. in vitro or in vivo for about5 minutes or less.

In certain embodiments, prior to being balloon-expanded (e.g., to anintended deployment diameter), the biodegradable stent is capable ofradially self-expanding, or radially self-expands, by about 0.025 inch(about 635 microns) or less, or by about 25% or less of the initialcrimped diameter, after being in aqueous condition (e.g., in aqueoussolution, water, saline solution or physiological conditions) at about37° C. in vitro or in vivo for about 5 minutes or less.

In other embodiments, prior to being balloon-expanded (e.g., to anintended deployment diameter), the biodegradable stent is capable ofradially self-expanding, or radially self-expands, by more than about0.025 inch (about 635 microns), or by more than about 25% of the initialcrimped diameter, after being in aqueous condition (e.g., in aqueoussolution, water, saline solution or physiological conditions) at about37° C. in vitro or in vivo for about 15 minutes or less, or about 10minutes or less, or about 5 minutes or less.

Further embodiments of the disclosure relate to a biodegradable stentcomprising a body which comprises a biodegradable polymer, wherein priorto being balloon-expanded, the stent is capable of radiallyself-expanding by about 0.001-0.025 inches, or about 0.003-0.015 inches,or about 0.005-0.10 inches, or about 0.001 inches or more, or about0.003 inches or more, or about 0.005 inches or more, or about 0.010inches or more, or about 0.025 inch (about 635 microns) or more, or byabout 0.25% or more of an initial crimped diameter of the stent, afterbeing in aqueous condition at about 37° C. in vitro or in vivo for about1 minute or less, or about 5 minutes or less, or about 15 minutes orless.

In some embodiments, prior to being balloon-expanded, the stent radiallyself-expands by about 0.001-0.025 inches, or about 0.003-0.015 inches,or about 0.005-0.10 inches, or about 0.001 inches or more, or about0.003 inches or more, or about 0.005 inches or more, or about 0.010inches or more, or about 0.025 inch (about 635 microns) or more, or byabout 0.25% or more of the crimped diameter of the stent, after being inaqueous condition at about 37° C. in vitro or in vivo for about 1 minuteor less, or about 5 minutes or less, or about 15 minutes or less.

In some embodiments, the stent is secured in place at least in part frommoving at least in one longitudinal direction by about 0.5 mm or less,or about 1 mm or less, or about 2 mm or less, or about 5 mm or less, byvarious means. Such means include at least one of configuring anexpandable member proximal and/or distal to the stent, configuring a nonexpandable member or stops proximal and/or distal to the stent,configuring an attachment or adhesive means adjacent to the stent thatdoes not prevent the stent from being balloon expandable, or configuringa sleeve that ends proximal to the stent, on top of the sent or distalto the stent. In an embodiment wherein the stent constraining means areexpandable member proximal and/or distal to the stent and wherein theexpandable means is deflated or collapsed at least partially prior toremoving the delivery system into the guide.

In a further embodiment, the biodegradable stent comprising a body whichcomprises a biodegradable copolymer, polymer blends, polymer blocks,polymeric mixtures (with a combination of two or more polymers) whereinsuitable copolymers, including the ones described herein, but notlimited to the disclosed copolymers, are configured to be capable ofbeing balloon expandable and self expanding, wherein prior to beingballoon-expanded, the stent self-expands by about 0.001-0.025 inches, orabout 0.003-0.015 inches, or about 0.005-0.10 inches, or about 0.001inches or more, or about 0.003 inches or more, or about 0.005 inches ormore, or about 0.010 inches or more, or about 0.025 inch (about 635microns) or more, or by about 0.25% or more of an initial crimpeddiameter of the stent, after being in aqueous condition at about 37° C.in vitro or in vivo for about 1 minute, or about 5 minutes or less, orabout 15 minutes or less.

In some embodiments, the biodegradable implantable devices (e.g., astent) comprising a polymeric material or body (e.g., a tubular body),wherein the material has a wet or dry glass transition temperature(T_(g)) of about 10° C. to about 70° C., or about 35° C. to about 70°C., or about 40° C. to about 60° C., or about 45° C. to about 55° C., orabout 45° C. to about 50° C., or about 37° C. to about 70° C., or about37° C. to about 60° C., or about 37° C. to about 55° C., or about 37° C.to about 50° C., or about 37° C. to about 45° C., or greater than 37° C.to about 70° C., or greater than 37° C. to about 60° C., or greater than37° C. to about 55° C., or greater than 37° C. to about 50° C., orgreater than 37° C. to about 45° C., or greater than 37° C. to less than45° C., or greater than 36° C. to less than 45° C., or greater than 36°C. to less than 40° C., or about 30° C. to about 70° C., or about 30° C.to about 60° C., or about 30° C. to about 50° C., or about 30° C. toabout 45° C. In another embodiment the biodegradable stent comprises atubular body which comprises a biodegradable polymer material; havingcrystallinity and glass transition temperatures as described in thisapplication.

In further embodiments, the one or more materials comprising the body,or the stent, or the stent material, or the tubular body or thepolymeric material may have a wet or dry glass transition temperature(T_(g)) greater than 20° C., or greater than 30° C., or greater than 31°C., or greater than 32° C., or greater than 33° C., or greater thanabout 34° C., or greater than 35° C., or greater than 36° C., or greaterthan 37° C. In some embodiments, the one or more materials comprisingthe body, or the stent, or the tubular body have a T_(g) less than 45°C., or less than 44° C., or less than 43° C., or less than 42° C., orless than 41° C., or less than 40° C., or less than 39° C., or less than38° C., or less than 37° C., or less than 36° C. In some embodiments,the one or more materials comprising the body, or the stent, or thetubular body have a T_(g) of about 20° C. to about 55° C., or about 20°C. to about 50° C., or about 31° C. to about 45° C., or about 32° C. toabout 45° C., or about 33° C. to about 45° C., or about 34° C. to about45° C., or about 35° C. to about 45° C., or about 36° C. to about 45°C., or about 37° C. to about 45° C., or about 38° C. to about 45° C., orabout 39° C. to about 45° C., or about 40° C. to about 45° C. In someembodiments, the one or more materials comprising the body, or thestent, or the tubular body have a T_(g) of about 20° C. to about 45° C.,or about 30° C. to about 44° C., or about 30° C. to about 43° C., orabout 30° C. to about 42° C., or about 30° C. to about 41° C., or about30° C. to about 40° C., or about 30° C. to about 39° C., or about 30° C.to about 38° C., or about 30° C. to about 37° C. In some embodiments,the one or more materials comprising the body, or the stent, or thetubular body has a T_(g) greater than 37° C. and less than 45° C., orgreater than 37° C. and less than 40° C., or greater than 37° C. to lessthan 50° C., or greater than 37° C. to less than 55° C.

In certain embodiments, the material comprising the body of the deviceor the biodegradable copolymer or the stent, has a degree ofcrystallinity of about 0% to about 40% and a T_(g) of about or greaterthan 37° C. to about 60° C. In certain embodiments, the materialcomprising the body of the device or the biodegradable copolymer or thestent has a degree of crystallinity of about 0% to about 30% and a T_(g)of about or greater than 37° C. to about 55° C. In certain embodiments,the material comprising the body of the device or the biodegradablecopolymer or the stent has a degree of crystallinity of about 0% toabout 30% and a T_(g) of about or greater than 37° C. to about 45° C. Incertain embodiments, the material comprising the body of the device orthe biodegradable copolymer or the stent has a degree of crystallinityof about 0% to about 30% and a T_(g) of about or greater than 10° C. toabout 35° C.

The biodegradable stent prosthesis comprising a tubular body comprisinga biodegradable polymeric material, wherein the tubular body has beenformed using extrusion, molding, dipping, or spraying, saidbiodegradable polymeric material has an initial crystallinity and has aTg greater than 37° C. and the stent prosthesis has a crystallinity(biodegradable stent material) lower than the initial crystallinity andat body temperature is radially expandable and has sufficient strengthto support a body lumen.

In another embodiment of any of the above embodiments, the Tg is greaterthan 30° C. and less than 60° C., preferably greater than 30° C. andless than 55° C., preferably greater than 30° C. and less than 45° C.,more preferably greater than 30° C. and less than 40° C., or morepreferably greater than 30° C. and less than 37° C.

In still further embodiments, the material (e.g., polymeric material)comprising the body of the device or the biodegradable copolymer orpolymer has a glass transition temperature (T_(g)) of at least about 10°C., 15° C., 20° C., 25° C., 30° C., 35° C., 37° C., 38° C., 40° C., 45°C., 50° C., 55° C., 60° C., 65° C. or 70° C. In some embodiments, thematerial (e.g., polymeric material) comprising the body of the device orthe biodegradable copolymer has a T_(g) of about 10° C., 35° C., 37° C.or 38° C. to about 70° C.; or about 10° C., 35° C., 37° C. or 38° C. toabout 65° C.; or about 10° C., 35° C., 37° C. or 38° C. to about 60° C.;or about 10° C., 35° C., 37° C. or 38° C. to about 55° C.; or about 10°C., 35° C., 37° C. or 38° C. to about 50° C. In certain embodiments, thematerial (e.g., polymeric material) comprising the body of the device orthe biodegradable copolymer has a T_(g) of about 35° C. to about 70° C.,or about 45° C. to about 60° C., or about 45° C. to about 55° C. Infurther embodiments, the material (e.g., polymeric material) comprisingthe body of the device or the biodegradable copolymer has a T_(g) ofabout 10° C. to about 37° C., or about 40° C. to about 60° C.

In some embodiments, the Tg refers to the Tg of the tubular body or thepolymeric material in a pellet form or after forming the tubular body orbefore treatment(s) or after treatment(s) or prior to implantation.

In some embodiments, when the treatment or modification is by heating,said heating can be at about Tg or below Tg, and the treatment(s) isprior to patterning or after patterning.

In other embodiments, the heat treatment or modification can be duringpatterning, such as during laser patterning.

In some embodiments, the Tg refers to the Tg of the tubular body or thepolymeric material as a pellet or after forming the tube, or the Tg ismeasured prior to the treatment or modification, or the Tg is measuredafter the treatment or modification, or the Tg is measured prior toimplantation.

In other embodiments, it is desired to control Tg to a desired rangefrom 30° C. to 60° C., preferably 35° C. to 55° C., more preferably from37° C. to 50° C., more preferably greater than 37° C. to 50° C. Thisallows for fabrication of a stent prosthesis capable of radial expansionat body temperature, or above body temperature, or below bodytemperature. Examples of controlling Tg (e.g., lowering it) can beaccomplished through additives such as plasticizers and monomers,presence or addition of solvents (such water, DCM, ethanol), andradiation. Controlling Tg (e.g., increasing it) can be accomplished byheating the material (below Tg, Tg, or above Tg), pressurizing thematerial, removing additives or plasticizers or solvents, and sometimes(depending on the material) through radiation. Control of radiation,increase or decrease or maintaining it, from substantially maintainingit the same from after forming to prior to implant, or increasing itfrom forming to prior to implant, or decreasing it from forming to priorto implant. In some embodiments Tg changes ranging from 0% change in Tgto 100% change in Tg, preferably from 5% to 50%, and more preferably 10%to 25%. In other embodiment, Tg changes by at least 0% from initial Tg,or by at least 10% of the initial or original Tg, and more preferably Tgchanges by at least 25% of the original Tg.

In one embodiment, the biodegradable stent prosthesis comprising atubular body comprising a biodegradable polymeric material, wherein thetubular body has been formed using extrusion, molding, dipping, orspraying, said biodegradable polymeric material has been treated tocontrol Tg to between 35° C. to 55° C., and the stent prosthesis at bodytemperature is radially expandable and has sufficient strength tosupport a body lumen.

In additional embodiments, the material (e.g., polymeric material)comprising the body of the device or the biodegradable polymer orcopolymer has a melting enthalpy (ΔH_(m)) of about 7 J/g to about 50J/g, or about 7 J/g to about 45 J/g, or about 7 J/g to about 40 J/g, orabout 20 J/g to about 45 J/g, or about 20 J/g to about 40 J/g, or about20 J/g to about 35 J/g, or about 25 J/g to about 35 J/g. In anembodiment, the material (e.g., polymeric material) comprising the bodyof the device or the biodegradable copolymer or polymer has a ΔH_(m) ofabout 7 J/g to about 50 J/g.

In further embodiments, the material (e.g., polymeric material)comprising the body of the device or the biodegradable copolymer orpolymer has a crystallization enthalpy (ΔH_(c)) less than about 5 J/g,or less than about 3 J/g, or less than about 1 J/g, or of about 0 J/g,during first heating. In yet further embodiments, the material (e.g.,polymeric material) comprising the body of the device or thebiodegradable copolymer or polymer has a crystallization enthalpy lessthan about 5 J/g, or less than about 3 J/g, or less than about 1 J/g, orof about 0 J/g, during first cooling. In certain embodiments, thematerial (e.g., polymeric material) comprising the body of the device orthe biodegradable copolymer or polymer has a ΔH_(c) less than about 5J/g during first heating and a ΔH_(c) less than about 5 J/g during firstcooling.

In another embodiment, it is desired to control crystallinity in amanner to preserve the material properties after forming. For example itis desirable to treat the tubular body or the biodegradable polymericmaterial wherein the crystallinity of the tubular body after forming issubstantially unchanged from the crystallinity of the stent prosthesismaterial prior to implant. In such cases, the treatment(s) of thebiodegradable polymeric material controls maintaining crystallinity tobe substantially the same.

In another embodiment, it is desired to control crystallinity in amanner to lower crystallinity after forming. For example it is desirableto treat the tubular body or the biodegradable polymeric materialwherein the crystallinity of the stent prosthesis material prior toimplant is lower than the crystallinity of the tubular body afterforming.

The biodegradable stent prosthesis comprising a tubular body comprisinga biodegradable polymeric material, wherein the tubular body has beenformed using extrusion, molding, dipping, or spraying, saidbiodegradable polymeric material has an initial crystallinity and has aTg greater than 37° C., and the stent prosthesis has a crystallinity(biodegradable stent material) that is substantially the same as theinitial crystallinity and at body temperature is radially expandable andhas sufficient strength to support a body lumen.

The biodegradable stent prosthesis comprising a tubular body comprisinga biodegradable polymeric material, wherein the tubular body has beenformed using extrusion, molding, dipping, or spraying, saidbiodegradable polymeric material has an initial crystallinity and has aTg greater than 37° C., and the stent prosthesis has a crystallinity(biodegradable stent material) lower than the initial crystallinity andat body temperature is radially expandable and has sufficient strengthto support a body lumen.

In another embodiment of any of the above embodiments, the Tg is greaterthan 30° C. and less than 60° C., preferably greater than 30° C. andless than 55° C., preferably, greater than 30° C. and less than 45° C.,more preferably greater than 30° C. and less than 40° C., or morepreferrably greater than 30° C. and less than 37° C.

A measure of residual/internal stress in a polymeric article or a deviceis shrinkage of the polymeric article or the device in a direction(e.g., longitudinal direction and/or radial direction) over a period oftime when the polymeric article or the device is heated over that periodof time at about the T_(g) or above the T_(g) or below the T_(g) of thematerial comprising the polymeric article or the body of the device. Insome embodiments, a tube comprised of a biodegradable polymeric materialor a stent formed from such a tube exhibits shrinkage in length of nomore than about 25%, 20%, 15%, 10% or 5%, and/or shrinkage in diameterof no more than about 25%, 20%, 15%, 10% or 5%, over a period of time(e.g., about 0.1, 12, 24, 48 to about 72 hours) when the tube or thestent is heated over that period of time at about the T_(g), or aboveT_(g), or below T_(g) (e.g., about 5° C., 10° C., 20° C. or 30° C.above) the T_(g) of the polymeric material comprising the tube or thestent body, or (e.g., about 5° C., 10° C., 20° C., or 30° C.) below theT_(g) of the polymeric material comprising the tube or the stent body.In certain embodiments, a tube comprised of a biodegradable polymericmaterial or a stent formed from such a tube exhibits shrinkage in lengthof no more than about 10% or 5%, and/or shrinkage in diameter of no morethan about 10% or 5%, over a period of time (e.g., about 1, 12, or 24hours) when the tube or the stent is heated over that period of time atabout the T_(g) or above (e.g., about 10° C. or 20° C. to about 30° C.above) the T_(g), or below Tg (e.g., about 5° C., 10° C., to about 30°C. below T_(g) of the polymeric material comprising the tube or thestent body.

In a further embodiment, the biodegradable stent comprising a body whichcomprises a biodegradable copolymer, polymer blends, polymer blocks,polymeric mixtures (with a combination of two or more polymers) whereinsuitable copolymers, including the ones described herein, but notlimited to the disclosed copolymers, are configured to be capable ofballoon expandable and self expanding, wherein prior to beingballoon-expanded, the stent radially self-expands by about 0.001-0.025inches, or about 0.003-0.015 inches, or 0.005-0.10 inches, or about0.001 inches or more, or about 0.003 inches or more, or about 0.005inches or more, or about 0.010 inches or more, or about 0.025 inch(about 635 microns) or more, or by about 0.25% or more of an initialcrimped diameter of the stent, after being in aqueous condition at about37° C. in vitro or in vivo for about 1 minute or less, or about 5minutes or less, or about 15 minutes or less, and wherein the stent orthe stent body has one or more of the following properties and retainsone or more such properties during a period of use: radial strength ofabout 5 psi to about 20 psi, or about 5 psi or greater, or about 10 psior greater, or about 15 psi or greater; recoil of about 3%-10% or about10% or less; % elongation at break of about 50%, or about 100%-about600%, or about 50% to about 300%; Tg of about 37° C.-60° C. or Tg ofabout 45° C.-55° C., after being in aqueous condition at about 37° C. invitro or in vivo for about 1 minute or less, or about 5 minutes or less,or about 15 minutes or less. Other applicable properties are describedin the disclosure herein.

In further embodiments, the stent self expands to a diameter that isless than the final intended deployment diameter of the stent prior tobeing balloon expanded to the final intended deployment diameter afterbeing in aqueous condition at about 37° C. in vitro or in vivo for about1 minute or less, or about 5 minutes or less, or about 15 minutes orless.

In some embodiments, the properties described herein with respect to thematerial (e.g., polymeric material) such as inherent viscosity, tensilestrength, percent elongation at break or yield, and ductility are in theranges stated prior to deployment of the stent, or after deployment ofthe stent.

A partially self-expandable stent can be retained on a balloon-catheterby any suitable means, including any means described herein. Such astent can be restrained from prematurely self-expanding by partially orfully covering the stent with a sheath or other constraining means.After the stent is delivered to an intended site of deployment, thesheath or other constraining means can be withdrawn or removed to allowthe stent to radially self-expand prior to balloon-expansion to anintended deployment diameter.

Partial self-expansion of a stent can be promoted or controlled by anyof a variety of ways. For example, the body of the stent can becomprised of a polymeric material that has a T_(g) closer to but abovebody temperature. The stent polymeric material having a T_(g) closer tobut above body temperature can control self-expansion of the stent.Having some differentiation between the T_(g) of the stent polymericmaterial and body temperature can prevent self-expansion of a crimpedstent that has some memory of the larger diameter of the polymeric tubefrom which it was patterned, as soon as the stent reaches bodytemperature. Water permeability of the polymeric material comprising thestent body can promote self-expansion of the stent, as water absorptioninto the stent body can cause the stent to swell and self-expand.Coating the stent with a material that is more crystalline or reduceswater absorption, or incorporating an additive in the coating of thestent which reduces water absorption or reacts with water, can controlself-expansion of the stent. Moreover, exposing the crimped stent to lowheat (e.g., about 20° C. to about 35° C. for at least about 5, 12, 24,36, 48 or 72 hours, or about 30° C. for at least about 2, 8, 16 or 24hours) can control self-expansion of the stent when in aqueous conditionat about 37° C. in vitro or in vivo.

In some embodiments, the biodegradable stent is capable of being crimpedto, e.g., inner (luminal)] diameter of about 0.5 mm to about 4 mm, orabout 1 mm to about 2 mm, or about 1.2 mm to about 1.6 mm, or about 1.3mm to about 1.5 mm, and is capable of being radially expanded, e.g., inaqueous condition (e.g., in aqueous solution, water, saline solution orphysiological conditions) at about 37° C. in vitro or in vivo, to a(e.g., inner) diameter of about 2 mm to about 8 mm, or about 2 mm toabout 6 mm, or about 2 mm to about 4 mm, or about 2.5 mm to about 4 mm,or about 2.7 mm to about 3.8 mm, or about 3 mm to about 3.6 mm, withoutsubstantial damage to struts, crowns or links of the stent, or withoutbreakage/fracture to struts, crowns or links of the stent, or withoutsubstantial recoil, or all three. In certain embodiments, the stent iscapable of being crimped to a (e.g., inner) diameter of about 1.2 mm toabout 1.6 mm and is capable of being radially expanded, e.g., in aqueouscondition (e.g., in aqueous solution, water, saline solution orphysiological conditions) at about 37° C. in vitro or in vivo, to a(e.g., inner) diameter of about 2.5 mm to about 4 mm without substantialdamage to struts, crowns or links or without substantial recoil, orboth.

In further embodiments, the biodegradable stent is capable of beingradially expanded, e.g., in aqueous condition (e.g., in aqueoussolution, water, saline solution or physiological conditions) at about37° C. in vitro or in vivo, to an initial deployment diameter and thento a second deployment diameter that is about 1% to about 300%, or about10% to about 300%, or about 10% to about 100%, or to a greater than theinitial deployment diameter, wherein the stent is uniformly expanded; orwithout substantial damage and/or without fracture/breakage to struts,crowns or links of the stent or/and without substantial recoil; or atleast some.

In additional embodiments, the biodegradable stent is capable of beingradially expanded to an intended deployment diameter. e.g., in aqueouscondition (e.g., in aqueous solution, water, saline solution orphysiological conditions) at about 37° C. in vitro or in vivo with about50% or less of crowns of the stent having a crack length of about 50% ofthe local crown width or shorter, or about 40% or less of the crownshaving a crack length of about 40% of the local crown width or shorter,or about 30% or less of the crowns having a crack length of about 30% ofthe local crown width or shorter, or about 25% or less of the crownshaving a crack length of about 25% of the local crown width or shorter,or about 20% or less of the crowns having a crack length of about 20% ofthe local crown width or shorter, or about 10% or less of the crownshaving a crack length of about 10% of the local crown width or shorter,or about 5% or less of the crowns having a crack length of about 5% ofthe local crown width or shorter. In certain embodiments, the stent iscapable of being radially expanded to an intended deployment diameter,e.g., in aqueous condition (e.g., in aqueous solution, water, salinesolution or physiological conditions) at about 37° C. in vitro or invivo, with about 25% or less of the crowns having a crack length ofabout 25% of the local crown width or shorter. In certain embodiment,the stent is capable of being deployed to an expanded diameter rangingfrom about 2 mm to about 4 mm in aqueous environment at 37° C. withoutbreakage (fracture) in any of the struts, crowns, or links. In yetanother embodiment, the stent prosthesis is capable of uniform radialexpansion to an intended diameter from a crimped state without cracks,or without fracture/breakage in any of the links, struts, or crowns.

Cracking or fracture of a structure (e.g., a stent) can be analyzed byany suitable method known in the art, including without limitation byvisualization using a microscope, optical comparator or scanningelectron microscope.

Cracking or fracture of a biodegradable polymeric stent can be reducedby any of a variety of ways. For example, treatment of the polymericmaterial, control of one of Tg, crystallinity, and molecular weight.Additional treatment, design, or control of material properties include:making the body of the stent from a polymeric material that is ductileand tough under physiological conditions can reduce cracking of thestent. Water permeability of the stent polymeric material can alsoreduce cracking (and improve radial strength) of the stent. When waterpermeates into the stent body, it can swell the polymeric material ofthe body, which can reduce the brittleness of the polymeric material.Further, designing the stent to have a longer radius of curvature canreduce cracking or fracture/breakage. Moreover, minimizing exposure ofthe crimped stent to heat (in terms of, e.g., temperature and exposuretime), as described herein with respect to reducing recoil, can decreasecracking of the stent. In some embodiment, the stent is at leastpartially configured to radially self expand to decrease cracking orbreakage of struts, crowns, or links upon deployment of the stent.

The conditions and manner in which the stent is radially expanded canalso affect cracking (and radial strength and recoil) of the stent.Other means of reducing cracking include without limitation allowing thestent to reach approximately body temperature, or within about 2° C. toabout 25° C. of body temperature, prior to balloon radial expansion,and/or allowing time (e.g., at least about 0.1, 0.25, 0.5, 1, 2, 3, 4 or5 minutes) for the stent to heat or/and absorb water into the stentprior to balloon radial expansion. Moreover, cracking or fracture can bedecreased by radially expanding the stent substantially uniformly suchthat crowns of the stent open at a substantially similar angle, orwithin 50 degrees of one another. Furthermore, cracking or fracture canbe reduced by maintaining a balloon-expanded stent at the radiallyexpanded state with the balloon inflated for a longer time (e.g., atleast about 0.1, 0.25, 0.5, 1, 2, 3, 4 or 5 minutes), and/or using astent-delivery catheter (e.g., Lifestream™ catheter from Abbott) thatallows blood to flow through while the balloon is inflated for a longertime (e.g., about 1, 3 or 5 or more minutes).

If the stent is a balloon-expandable stent (whether partiallyself-expandable or not), a slow rate of inflation of the balloon in thebeginning of balloon-assisted expansion can reduce cracking. Forexample, a 3 mm stent can be deployed (radially expanded to the intendeddeployment diameter) by inflation of the balloon to about 6 to 16atmospheres of pressure. During the first about 2 to 3 atmospheres ofpressure, the rate of inflation of the balloon can be about 2 or 5 toabout 20 seconds per atmosphere, or about 7 to about 15 seconds peratmosphere. Thereafter the balloon can be inflated at a faster rate(e.g., about 0.1 to about 5 seconds per atmosphere). After the stent isradially expanded to the intended deployment diameter, the pressure ofthe balloon can be maintained for a period of time, e.g., for at leastabout 0.1, 0.25, 0.5, 1, 2 or 3 minutes. A stent-delivery catheter(e.g., Lifestream™ catheter) that allows blood to flow through while theballoon is inflated can be employed.

Exposure of the stent to a temperature substantially equal to or abovebody temperature prior to and/or during radial expansion can alsodecrease cracking or fracture of the stent. In certain embodiments,prior to and/or during radial expansion the stent is exposed to atemperature at least about 1° C., 4° C., 8° C., 12° C. or 16° C. abovebody temperature, or to a temperature within about 20° C., 15° C., 10°C. or 5° C. of the T_(g) (below or above the T_(g)), or equal to orabove the T_(g), of the material (e.g., polymeric material) comprisingthe body of the stent. Exposure of the stent to a temperaturesubstantially equal to or above body temperature can be accomplished byany of a variety of means, such as use of a heating coil or element(s)in the balloon, use of heating element(s) on the surface of the balloonor the proximal shaft of the delivery catheter, heating of a liquidinside the balloon, introduction of a heated liquid into the balloon, orintroduction of a heated aqueous (e.g., saline) solution into the bodilyfluid (e.g., blood stream) at the site of stent deployment.

In some embodiments, fatigue of a stent is measured by the appearance ofa certain number of pieces (e.g., one piece) missing from the stent, orthe appearance of a certain number of fractures (e.g., two fractures),or the appearance of a certain number of cracks (e.g., three cracks),optionally under certain conditions, e.g., in dry condition or inaqueous condition (e.g., aqueous solution, water, saline solution orphysiological conditions) at a certain temperature (e.g., ambienttemperature or about 37° C.) in vitro or in vivo, and optionally over acertain period of time (e.g., about 1 minute to about 1, 2 or 3 weeks,or about 1, 2, 3, 4, 5 or 6 months). In certain embodiments, a crack iscracking that does not extend through the whole width of a crown, and afracture is cracking that extends through the whole width or depth of acrown, strut, or a link, thereby breaking the crown, strut, or link.

In further embodiments, fatigue of a stent is measured based on thenumber of cycles (or the number of months of fatigue) before theappearance of a certain number of pieces (e.g., one piece) missing fromthe stent. Fatigue testing can be conducted under real-time oraccelerated condition. In a real-time test, the stent can be subjectedto a cyclic loading of, e.g., about 1 to 2 Hz (about 60 to 120 cyclesper minute, substantially similar to a human heart beat). The test canbe conducted for about 1, 2 or 3 months or longer to simulate the timeperiod of implantation in a subject. The stent can be tested in vitro ina tube that has a radial compliance of, e.g., about 3% to 5% (the tubecould radially expand by about 3% to 5%), which is substantially similarto the compliance of an artery. Under accelerated condition, the stentcan be subjected to a cyclic loading greater than about 2 Hz (e.g.,about 30 Hz). At 30 Hz, it would take about 6 days of continuouscycling, compared to about 90 days at 2 Hz, to attain about 3 months offatigue. In some embodiments, the stent does not exhibit missing piecesor complete fracture of a link, a strut, or a crown after fatiguetesting at one of the above conditions from about 1 day to about 6months, or from about one week to about one month or from about 2 weeksto about 3 months.

Resistance of a stent to fatigue (or fatigue strength) can be enhancedby any of a variety of ways. For example, fatigue resistance/strengthcan be increased by making the stent from a polymeric material that isductile and tough under physiological conditions, and/or by configuringthe stent to be capable of radially self-expanding prior to balloonexpansion to an intended deployment diameter. As another example,fatigue resistance/strength can be enhanced by the pattern or design ofthe stent, by decreasing the sharpness (or increasing the smoothness) ofedges of crowns of the stent, and/or by increasing the uniformity of thecross-section of the crowns. As a further example, fatigueresistance/strength can be increased by minimizing exposure of the stentto extremely high temperature or extremely low temperature, and/or byminimizing bending and other stresses on the stent (e.g., when the stentis at, below or above body temperature).

In some embodiments, the biodegradable stent has a radial strength of atleast about 5, 7, 10, 12, 14, 15, 16, 18, 20, 22, 24, 25 or 30 psi inaqueous condition (e.g., in aqueous solution, water, saline solution orphysiological conditions) at about 37° C. in vitro or in vivo. Incertain embodiments, the stent has a radial strength of about 5 psi toabout 30 psi, or about 5 psi to about 25 psi, or about 10 psi to about25 psi, or about 12 psi to about 23 psi, or about 10 psi to about 20psi, or about 15 psi to about 20 psi, or about 16 psi to about 22 psi,in aqueous condition (e.g., in aqueous solution, water, saline solutionor physiological conditions) at about 37° C. in vitro or in vivo. Incertain embodiments, the stent has a radial strength of about 5 psi toabout 30 psi, or about 10 psi to about 25 psi, in aqueous condition(e.g., in aqueous solution, water, saline solution or physiologicalconditions) at about 37° C. in vitro or in vivo.

Radial strength of a biodegradable polymeric stent can be improved inany of a variety of ways. As an example, making the stent body from apolymeric material that is ductile and tough under physiologicalconditions can enhance the radial strength of the stent. Further, radialstrength can be increased by orienting the stent polymeric material, orthe crystals, crystalline regions or chains of the polymeric material,substantially in the circumferential direction. For example, prior topatterning the stent from a polymeric tube, the tube can be radiallyexpanded, optionally while the tube is heated at elevated temperature(e.g., at or above the T_(g) of the tube polymeric material) andoptionally with cooling of the radially expanded tube to a lowertemperature (e.g., below T_(g)), to impart substantially circumferentialorientation or biaxial (neither preferentially circumferential norpreferentially longitudinal) orientation to the polymeric material, orits crystals, crystalline regions or polymer chains. Crimping the stentto a smaller diameter under certain conditions can minimize radialstrength loss upon expansion of the stent. In one embodiment, the stentis crimped gradually at a temperature ranging from about 25° C. to about50° C. in 10 seconds to about 10 minutes.

The conditions and manner in which the stent is radially expanded canalso affect the radial strength of the stent. Non-limiting conditionsand ways in which the stent can be radially expanded to improve radialstrength are described with respect to reducing cracking or improvingstent expanded uniformity.

In further embodiments, the biodegradable stent exhibits a percentageradially inward recoil of about 15% or less, or about 12% or less, orabout 10% or less, or about 8% or less, or about 6% or less, or about 5%or less, or about 4% or less, or about 3% or less, after a period oftime (e.g., about 1, 3 or 5 days, or about 1, 2 or 3 weeks, or about 1,2 or 3 months) after being radially expanded to an intended deploymentdiameter in aqueous condition (e.g., in aqueous solution, water, salinesolution or physiological conditions) at about 37° C. in vitro or invivo. In certain embodiments, the stent exhibits a percentage radiallyinward recoil of about 10% or less, or about 8% or less, about one weekto about one month after being radially expanded to an intendeddeployment diameter in aqueous condition (e.g., in aqueous solution,water, saline solution or physiological conditions) at about 37° C. invitro or in vivo.

Recoil of the stent can be reduced by any of a variety of ways. Forexample, the body of the stent can be comprised of a polymeric materialthat is ductile and tough under physiological conditions, has a T_(g)that is not too high (e.g., about 60° C., 55° C., 50° C. or lower),and/or has a molecular weight of at least a certain value (e.g., aweight-average molecular weight of at least about 120 kDa, 150 kDa, 180kDa, 210 kDa, 240 kDa, 500 kDa, or 900 kDa). In some embodiments, recoilof a stent comprised of a polymeric material having molecular weight inthe range of about 120 kDa to about 1200 kDa is less than 10% as aresult of greater entanglement of longer polymer chains. In someembodiments, the recoil of a stent comprised of a polymeric materialhaving molecular weight in the range of about 120 kDa to about 1200 kDais less than 10% as a result of greater entanglement of longer polymerchains. Greater entanglement of polymer chains can further reduce recoilof the polymeric tubular body having higher molecular weight.

In some embodiments, a stent is designed to have reduced recoil by beingconfigured to be fully self-expandable or be capable of radiallyself-expanding (e.g., by at least about 0.01 inch or 0.025 inch, or byat least about 10% or 25% of the initial crimped diameter) prior toballoon expansion to an intended deployment diameter. In certainembodiments, the body of a partially self-expandable stent is comprisedof a polymeric material that has a T_(g) of about 35° C. to about 55 or60° C., or about 37° C. to about 55 or 60° C., or about 40° C. to about50 or 55° C., or about 45° C. to about 50 or 55° C. In some embodiments,during the initial partial self-expansion of the stent (e.g., by atleast about 0.01 inch or 0.025 inch, or by at least about 10% or 25% ofthe initial crimped diameter), and/or during balloon expansion of thestent to an intended deployment diameter, the stent is exposed to atemperature within about 15° C., 10° C., 5° C. or 3° C. of the T_(g)(below or above the T_(g)), or at or above the T_(g). In furtherembodiments, the body of a fully self-expandable stent or a partiallyself-expandable stent is comprised of a polymeric material that has aT_(g) of about 10° C. to about 35 or 37° C., or about 15° C. to about 35or 37° C., or about 20° C. to about 30 or 35° C., or about 25° C. toabout 30 or 35° C. In certain embodiments, a partially or fullyself-expandable stent is patterned from a polymeric tube having adiameter greater than an intended deployment diameter or the maximumallowable expansion diameter of the stent, as described herein.

Recoil of a biodegradable stent can also be reduced by patterning thestent from a polymeric tube having a diameter (e.g., inner diameter)that is slightly smaller, same, or greater than (e.g., at least about−10%, −5%, 0%, 5%, 10%, 20%, 30%, 40% or 50%) the intended deployment(e.g., inner) diameter or the maximum allowable expansion (e.g., inner)diameter of the stent. After deployment in aqueous condition at about37° C., the stent can have a tendency or ability to self-expand overtime to the larger diameter of the tube from which the stent was cut ifthe stent is exposed to a temperature equal to or above the T_(g) of thepolymeric material comprising the stent body. The T_(g) of a polymericmaterial in aqueous condition (wet T_(g)) can be lower (e.g., about 1-5°C. lower, or about 1-10° C. lower, or about 1-15° C. lower, or about 5°C., 10° C. or 15° C. lower) than its dry T_(g). The stent's tendency orability to self-expand to the larger tube diameter can minimize orprevent radially inward recoil of the stent after deployment.

The conditions in which the stent is crimped, and the crimped stent istreated and handled, can affect recoil of the stent. For example, recoilcan be reduced by crimping the stent at a temperature at about the T_(g)or below the T_(g) (e.g., at least about 1° C., 5° C., 10° C., 15° C.,20° C., 25° C., 30° C., or 35° C. below the T_(g)) of the material(e.g., polymeric material) comprising the stent body. Minimizingexposure of the crimped stent to heat (in terms of, e.g., temperatureand exposure time), as described herein, can also reduce recoil (andreduce cracking and improve radial strength). Heat may promotegeneration of a crimped-state memory and may promote erasure of someamount of the as-cut tube memory (the diameter of the tube used topattern the stent). For example, recoil can be decreased by exposing thecrimped stent to a temperature not exceeding the T_(g), or at leastabout 1° C., 5° C., 10° C., 15° C., 20° C., 25° C. or 30° C. below theT_(g), of the material (e.g., polymeric material) comprising the stentbody during, e.g., stabilization of the stent in the crimped state,mounting of the crimped stent onto a balloon-catheter, sterilization ofthe stent delivery system (e.g., with e-beam), and storage.

The conditions and manner in which the stent is radially expanded canalso affect recoil of the stent. Non-limiting conditions and ways inwhich the stent can be radially expanded to reduce recoil are describedwith respect to reducing cracking.

In additional embodiments, the biodegradable stent exhibits reduction inlength of no more than about 25%, 20%, 15%, 10% or 5% after a period oftime (e.g., about 1, 3 or 5 days, or about 1, 2 or 3 weeks, or about 1,2 or 3 months) after being radially expanded to an intended deploymentdiameter in aqueous condition (e.g., in aqueous solution, water, salinesolution or physiological conditions) at about 37° C. in vitro or invivo. In certain embodiments, the biodegradable stent exhibits reductionin length of no more than about 10% about one week to about one monthafter being radially expanded to an intended deployment diameter inaqueous condition (e.g., in aqueous solution, water, saline solution orphysiological conditions) at about 37° C. in vitro or in vivo. In afurther embodiment, the biodegradable stent comprising a body whichcomprises a biodegradable polymer, or copolymer, polymer blends, polymerblocks, polymer mixture wherein the polymer material is configured to becapable of being balloon expandable and self expanding, wherein prior tobeing balloon-expanded, the stent self-expands by about 0.001-0.025inches, or about 0.003-0.015 inches, or about 0.005-0.10 inches, orabout 0.001 inches or more, or 0.003 inches or more, or 0.005 inches ormore, or 0.010 inches or more, or 0.025 inch or more, or by about 0.25%or more of an initial crimped diameter of the stent, after being inaqueous condition at about 37° C. in vitro or in vivo for about 1minute, or about 5 minutes or less, or about 15 minutes or less.

In a further embodiment, the biodegradable stent comprising a body whichcomprises a biodegradable copolymer or polymer, or mixture of 2-3polymers, or blend of polymers, or wherein the copolymer or polymer isconfigured to be capable of balloon expandable and self expanding,wherein prior to being balloon-expanded, the stent radially self-expandsby about 0.001-0.025 inches, or about 0.003-0.015 inches, or 0.005-0.10inches, or about 0.001 inches or more, or about 0.003 inches or more, orabout 0.005 inches or more, or about 0.010 inches or more, or about0.025 inch or more, or by about 0.25% or more of an initial crimpeddiameter of the stent, after being in aqueous condition at about 37° C.in vitro or in vivo for about 1 minute or less, or about 5 minutes orless, or about 15 minutes or less, and wherein the stent or the stentbody has one or more of the following properties: radial strength ofabout 5 psi to about 20 psi, or about 5 psi or greater, or about 10 psior greater, or about 15 psi or greater, recoil of about 3%-10% or about10% or less, or % elongation at break >50%, or about 100%-about 600%, orabout 50% to about 300%, or Tg of about 37° C.-60° C. or Tg of about 45°C.-55° C., after being in aqueous condition at about 37° C. in vitro orin vivo for about 1 minute or less, or about 5 minutes or less, or about15 minutes or less.

In further embodiments, the biodegradable stent comprising a body whichcomprises a biodegradable copolymer or polymer, wherein the copolymer orpolymer is configured to be balloon expandable and self expanding,wherein prior to being balloon-expanded, the stent radially self-expandsby about 0.025-0.25 inches, or about 0.50-0.15 inches, or about 0.025inches or more, or about 0.050 inches or more, or about 0.1 inches ormore, or by about 0.25% or more of an initial crimped diameter of thestent, after being in aqueous condition at about 37° C. in vitro or invivo for about 1 minute or less, or about 5 minutes or less, or about 15minutes or less. Optionally, the stent is constrained from selfexpanding using a sheath or other means and then such constraining meansis removed, disengaged, or withdrawn, or released after the stent ispositioned for deployment, allowing the stent to self deploy.

In further embodiments, the material comprising the body of the deviceor the biodegradable polymer, copolymer or polymer blend, or the tubularbody comprising the biodegradable polymer, or the stent; is, or hascrystals, crystalline regions, or polymer chains that are: substantiallynot uniaxially oriented, or circumferentially oriented, orlongitudinally oriented, or biaxially oriented. In other embodiments,the biodegradable copolymer has crystals, crystalline regions, moleculararchitecture, structural order, orientation, or polymer chains that are:substantially not uniform, or has low degree of order, or has varyingdegree of order, or is not substantially oriented as a result of notperforming at least one of pressurizing and stretching of the tubularbody, or is at least partially oriented as a result of spraying ordipping or crystallization or recrystallization, or radiation, or is atleast partially oriented as a result of solvent evaporation or annealingor radiation, or is substantially not oriented, or not uniformlyoriented, or low order oriented, or varying degree oriented, or randomlyoriented, as a result of spraying or dipping, or solvent evaporation, orannealing, or radiation, or crystallization or recrystallization. In yetanother embodiment, the biodegradable copolymer has crystals,crystalline regions, molecular architecture, structural order,orientation, or polymer chains that are: substantially oriented, ororiented, or biaxially oriented, or uniaxially oriented, or oriented ina direction that is longitudinal, or oriented in a direction that iscircumferential, or oriented in a direction that is not longitudinal orcircumferential, or oriented as a result of at least one of pressurizingthe copolymer tube or stretching or drawing the tube, or oriented as aresult of modification or treatment. In yet further embodiments, thematerial comprising the body of the device or the biodegradable polymer,or copolymer or polymer blend, or the tubular body comprising thebiodegradable polymer; has a tensile strength of at least about 2000psi, or at least about 2500 psi, or at least about 3000 psi, or at leastabout 4000 psi, or 5000 psi. In yet further embodiments, thebiodegradable polymeric material or the tubular body or the stent; hasstiffness of at least 1000 MPa, or at least 1500 MPa, or at least 2000MPa, or at least 2500 MPa, or at least 3000 MPa, or at most 5000 MPa, orat most 4000 MPa; when measured at ambient or body temperature. In yetfurther embodiments, the biodegradable polymeric material or the tubularbody or the stent; has elastic modulus of at least 250 MPa, or at least350 MPa, or at least 400 MPa, or at least 450 MPa, or at least 500 MPa;when measured at ambient or body temperature. In yet another embodiment,the material comprising the body or the biodegradable polymer orcopolymer or polymer blend, or the tubular body comprising thebiodegradable polymer, or the stent; has a percent elongation at breakof about 20% to about 600%, or of about 20% to about 300%, or of about20% to about 200%, or of about 20% to about 100%, or of about 20% toabout 50%, or of about 10% to about 600%, or of about 10% to about 300%,or of about 5% to about 600%, or of about 5% to about 300%, or of about1% to about 600%, or of about 1% to about 300%, or of about 1% to about200%, or of about 1% to about 150%; when measured wet or dry at ambienttemperature, or body temperature. In other embodiments, thebiodegradable polymer, copolymer or polymer blend or tubular bodycomprising the biodegradable polymer material or prosthesis hasstiffness dry or wet at about 37° C. of about 0.4N/mm2 to about 2N/mm2,or of about 0.5N/mm2 to about 1.5N/mm2, or of about 0.7N/mm2 to about1.4N/mm2, or of about 0.8N/mm2 to about 1.3N/mm2. In other embodiments,the biodegradable polymer or copolymer or polymer blend or tubular bodycomprising the biodegradable polymer material or prosthesis; has elasticmodulus dry or wet at about body temperature, of about 0.2 Pa to about20 Pa, or of about 0.3 Pa to about 5 Pa, or of about 0.4 to about 2.5Pa, or of about 0.5 Pa to about 1 Pa, or at least 0.2 Pa, or at least0.3 Pa, or at least 0.4 Pa, or at least 0.5 Pa. In other embodiments,the biodegradable polymer or copolymer or polymer blend or tubular bodycomprising the biodegradable polymer material or prosthesis; has yieldstrain of at most 15%, preferably at most 10%, more preferably at most5%, in water at 37° C. In yet another embodiment, the prosthesis hasradial strength sufficient to support a body lumen. In yet anotherembodiment, the biodegradable polymer or copolymer or tubular body orprosthesis; has a radial strength in an aqueous environment at about 37°C. of about 3 psi to about 25 psi, or of about 5 psi to about 22 psi, orof about 7 psi to about 20 psi, or of about 9 psi to about 18 psi. Inyet another embodiment, the biodegradable polymer or copolymer ortubular body or prosthesis; has a radial strength in an aqueousenvironment at body temperature of, greater than 3 psi, or greater than8 psi, or greater than 10 psi, or greater than 15 psi. Radial strengthcan be measured in a variety of methods known in the art. For examplethe flat plate method or iris method or other known methods. Radialforce can be measured with several methods known in the art. For examplewhen the stent radial strength is not sufficient to support a bodylumen, or the expanded diameter is reduced by a substantial amount, orreduced by at least 15%, or reduced by at least 20%, or reduced by atleast 25%, or reduced by at least 50%. In other embodiments, thebiodegradable copolymer, or polymer blend, or polymer, or tubular bodycomprising the biodegradable polymer, or prosthesis has a % recoil in anaqueous environment at 37° C. of about −20% to about 20%, or of about−15% to about 15%, or of about −10% to about 10%, or of about −10% toabout 0%, or of about 0% to about 10%, or of about 3% to about 10%, orof about 4% to about 9%, or less than 25%, or less than 20%, or lessthan 15%, or less than 10%, or less than 5%; after expansion from acrimped state. % recoil is measured in a variety of ways in-vitro orin-vivo with methods known in the art. For example in-vitro % recoil canbe measured by expanding the stent in an aqueous environment at about37° C. inside a tube or unconstrained and measuring % recoil afterexpansion using laser micrometer. For an example for in-vivo % recoilmeasurement using QCA see, e.g., Catheterization and CardiovascularInterventions, 70:515-523 (2007). In yet another embodiment, thebiodegradable polymer or copolymer or tubular body or prosthesis, has aradial strength (in an aqueous environment at 37° C. for about 1 minuteto about 1 day) of about 3 psi to about 25 psi; wherein the radialstrength increases by about 1 psi to about 20 psi, or by about 2 psi toabout 15 psi, or by about 3 psi to about 10 psi, or by about 4 psi toabout 8 psi, after being in such an aqueous environment for about 1 dayto about 60 days. In other embodiments, the biodegradable, polymer, orcopolymer, or polymer blend, or tubular body, or stent; is substantiallyamorphous, or substantially semi crystalline, or substantiallycrystalline; after modification, or before modification, or afterradiation, or before implantation into a mammalian body. In otherembodiments, the biodegradable polymer, or copolymer or polymer blend,or tubular body, or stent; is substantially amorphous before and aftermodification, or substantially amorphous before a modification andsubstantially semi crystalline after modification, or substantiallyamorphous before a modification and substantially crystalline aftermodification, or substantially semi crystalline before a modificationand substantially amorphous after modification, or substantially semicrystalline before a modification and substantially semi crystallineafter modification, or substantially semi crystalline before amodification and crystalline after modification, or substantiallycrystalline before modification and substantially semi crystalline aftera modification, or substantially crystalline before a modification andsubstantially amorphous after a modification, or substantiallycrystalline before a modification and after modification. In otherembodiments, the biodegradable polymer or copolymer or polymer blend ortubular body or implant has longitudinal shrinkage of about 0% to about30%, or of about 5% to about 25%, or of about 7% to about 20%, or ofabout 10% to about 15%; when heated (e.g. in an oven) at temperaturesranging from about 30° C. to about 150° C. (with or without a mandrelinserted into the copolymer or tubular body or prosthesis for a timeranging from about 30 minutes to about 24 hours), or upon expansion ofthe stent from a crimped state to an expanded state. In yet anotherembodiment, the longitudinal shrinkage is less than 30%, or less than25%, or less than 20%, or less than 15%, or less than 10%, of theoriginal length. In yet another embodiment, the stent or polymermaterial or polymer tube has longitudinal shrinkage of less than about25% or less, or about 15% or less, or about 10% or less, or about 5% orless, or about 1-25%, or about 5-15%, after being in aqueous conditionat about 37° C. in vitro or in vivo for about 1 minute or less, or about5 minutes or less, or about 15 minutes or less, or after expansion fromthe crimped state. In other embodiments the stent or polymer material orpolymer tube has longitudinal shrinkage of less than about 25% or less,or about 15% or less, or about 10% or less, or about 5% or less, orabout 1-25%, or about 5-15%, after being in aqueous condition at about37° C. in vitro or in vivo for about 1 minute or less, or about 5minutes or less, or about 15 minutes or less, or after expansion fromthe crimped state by configuring the polymer to be; more amorphous, orsubstantially amorphous, or reducing internal stresses, or reducing orminimizing orientation of the polymer, and/or optimizing design of thestent, or a combination thereof. In yet another embodiment, theamorphous, or semicrystalline, or crystalline polymer has internalstresses, or longitudinal shrinkage of no more than 15% from before amodification to after modification. In yet another embodiment, thepolymer comprises a polymer, or a co-polymer, or a blend of polymers, ora mixture of polymers, or a blend of polymer and at least one monomer,or a blend of co-polymer and at least one monomer, or a combinationthereof. In yet another embodiment, the polymer blend, copolymer, ormixture of polymers, substantially does not exhibit phase separation. Inyet another embodiment, the polymer or tubular body or prosthesis, isporous; such that it will grow in the radial direction by about 0.025 mmto about 1 mm when soaked in an aqueous environment at 37° C. from about1 minute to about 15 minutes. In another embodiment, the copolymermaterial, or tubular body, or prosthesis, has a textured surface, or nonuniform surface, or surface with ridges, or bumpy surface, or surfacewith grooves, or wavy surface. The distance between the peak and troughof the surface texture ranges from about 0.01 micron to about 30 micron,or from about 0.1 micron to about 20 micron, or from about 1 micron toabout 15 micron.

In certain embodiments, the yield strength of the material (e.g.,polymeric material) comprising the body of an endoprosthesis (e.g., astent) is at least about 50%, 60%, 70%, 75%, 80%, 90% or 95% of ultimatestrength in aqueous condition (e.g., in aqueous solution, water, salinesolution or physiological conditions) at about 37° C. in vitro or invivo. In an embodiment, the yield strength of the material (e.g.,polymeric material) comprising the body of the endoprosthesis (e.g.,stent) is at least about 75% of ultimate strength in aqueous condition(e.g., in aqueous solution, water, saline solution or physiologicalconditions) at about 37° C. in vitro or in vivo.

In some embodiments, the elastic modulus of the material (e.g.,polymeric material) comprising the body of an endoprosthesis (e.g., astent) is at least about 0.1, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7,8, 9 or 10 GPa in aqueous condition (e.g., in aqueous solution, water,saline solution or physiological conditions) at about 37° C. in vitro orin vivo. In certain embodiments, the elastic modulus of the material(e.g., polymeric material) comprising the body of the endoprosthesis(e.g., stent) is at least about 0.5 or 0.75 GPa in aqueous condition(e.g., in aqueous solution, water, saline solution or physiologicalconditions) at about 37° C. in vitro or in vivo.

In further embodiments, the elastic recovery of a strained material(e.g., polymeric material) comprising the body of an endoprosthesis(e.g., a stent) is at most about 20%, 18%, 16%, 15%, 14%, 12%, 10%, 8%,6%, 5%, 4% or 2% in aqueous condition (e.g., in aqueous solution, water,saline solution or physiological conditions) at about 37° C. in vitro orin vivo. In certain embodiments, the elastic recovery of a strainedmaterial (e.g., polymeric material) comprising the body of theendoprosthesis (e.g., stent) is at most about 15% or 10% in aqueouscondition (e.g., in aqueous solution, water, saline solution orphysiological conditions) at about 37° C. in vitro or in vivo.

In yet further embodiments, the yield strain of the material (e.g.,polymeric material) comprising the body of an endoprosthesis (e.g., astent) is at most about 15%, 14%, 12%, 10%, 8%, 6%, 5%, 4%, 3% or 2% inaqueous condition (e.g., in aqueous solution, water, saline solution orphysiological conditions) at about 37° C. in vitro or in vivo. In anembodiment, the yield strain of the material (e.g., polymeric material)comprising the body of the endoprosthesis (e.g., stent) is at most about10% in aqueous condition (e.g., in aqueous solution, water, salinesolution or physiological conditions) at about 37° C. in vitro or invivo.

In additional embodiments, the plastic strain of the material (e.g.,polymeric material) comprising the body of an endoprosthesis (e.g., astent) is at least about 10%, 20%, 30%, 40%, 50% or 60% in aqueouscondition (e.g., in aqueous solution, water, saline solution orphysiological conditions) at about 37° C. in vitro or in vivo. In anembodiment, the plastic strain of the material (e.g., polymericmaterial) comprising the body of the endoprosthesis (e.g., stent) is atleast about 30% in aqueous condition (e.g., in aqueous solution, water,saline solution or physiological conditions) at about 37° C. in vitro orin vivo.

In some embodiments, the radial strength of an endoprosthesis (e.g., astent) comprised of a biodegradable polymeric material is at least about5, 7, 10, 12, 14, 15, 16, 18, 20, 22, 24, 25 or 30 psi in aqueouscondition (e.g., in aqueous solution, water, saline solution orphysiological conditions) at about 37° C. in vitro or in vivo. Incertain embodiments, the radial strength of the endoprosthesis (e.g.,stent) is at least about 10 or 15 psi in aqueous condition (e.g., inaqueous solution, water, saline solution or physiological conditions) atabout 37° C. in vitro or in vivo.

In further embodiments, after being radially expanded to an intendeddeployed diameter in aqueous condition (e.g., in aqueous solution,water, saline solution or physiological conditions) at about 37° C. invitro or in vivo, an endoprosthesis (e.g., a stent) comprised of abiodegradable polymeric material retains at least about 25%, 30%, 40%,50%, 60%, 70%, 80%, 90% or 95% of its strength (e.g., radial strength)after a period of time (e.g., about 1, 3 or 5 days, or about 1, 2 or 3weeks, or about 1, 2 or 3 months). In an embodiment, the endoprosthesis(e.g., stent) retains at least about 50% of its strength (e.g., radialstrength) about one month after being radially expanded to an intendeddeployed diameter in aqueous condition (e.g., in aqueous solution,water, saline solution or physiological conditions) at about 37° C. invitro or in vivo.

In still further embodiments, after being radially expanded to anintended deployed diameter in aqueous condition (e.g., in aqueoussolution, water, saline solution or physiological conditions) at about37° C. in vitro or in vivo, an endoprosthesis (e.g., a stent) comprisedof a biodegradable polymeric material increases by at least about 5%,10%, 20%, 25%, 30%, 40% or 50% in strength (e.g., radial strength) aftera period of time (e.g., about 1, 2, 3, 4, 5 or 6 weeks). In anembodiment, the endoprosthesis (e.g., stent) increases by at least about10% in strength (e.g., radial strength) about one day to about two weeksafter being radially expanded to an intended deployed diameter inaqueous condition (e.g., in aqueous solution, water, saline solution orphysiological conditions) at about 37° C. in vitro or in vivo.

In additional embodiments, an endoprosthesis (e.g., a stent) comprisedof a biodegradable polymeric material exhibits a percentage radiallyinward recoil of about 15%, 12%, 10%, 8%, 6%, 5%, 4% or 3% or less aftera period of time (e.g., about 1, 3 or 5 days, or about 1, 2 or 3 weeks,or about 1, 2 or 3 months) after being radially expanded to an intendeddeployed diameter in aqueous condition (e.g., in aqueous solution,water, saline solution or physiological conditions) at about 37° C. invitro or in vivo. In certain embodiments, the endoprosthesis (e.g.,stent) exhibits a percentage radially inward recoil of about 10% orless, or about 8% or less, upon deployment, or after deployment, orabout one week to about one month after being radially expanded to anintended deployed diameter in aqueous condition (e.g., in aqueoussolution, water, saline solution or physiological conditions) at about37° C. in vitro or in vivo.

When the device is a stent, the stent can have any pattern and designsuitable for its intended use. The stent can be implanted in a subjectfor treatment of a wide variety of conditions, including obstruction ornarrowing of a vessel (e.g., blood vessel) or other tubular tissue ororgan in the body. In certain embodiments, the biodegradable stentexhibits a percentage radially inward recoil of about 20% or less, or ofabout 15% or less, or of about 10% or less, or of about 8% or less, orof about 6% or less, upon deployment or after deployment of the stent,or at any time ranging from about day 0 to about day 30 after deploymentin aqueous condition at about 37° C. in vitro or in vivo. In anembodiment, the stent exhibits percent recoil of about 10% or less afterdeployment, or after radial expansion in aqueous condition at about 37°C. in vitro or in vivo.

In one embodiment, the biodegradable stent prosthesis comprising atubular body comprising a biodegradable polymeric material, wherein thetubular body has been formed using extrusion, molding, dipping, orspraying, said biodegradable polymeric material has been treated tocontrol Tg to between 35° C. to 55° C., and the stent prosthesis at bodytemperature is radially expandable and has sufficient strength tosupport a body lumen and has a percent recoil lower than 15% from anexpanded state.

In further embodiments, the material (e.g., polymeric material)comprising the body of the device or the biodegradable copolymer orpolymer is ductile and tough. In yet further embodiments, the material(e.g., polymeric material) comprising the body of the device or thebiodegradable copolymer or polymer has high tensile strength or highelongation, or both. In some embodiments, the material (e.g., polymericmaterial) comprising the body of the device or the biodegradablecopolymer or polymer has a tensile strength of at least about 1000 psi(about 6.9 MPa), 2000 psi (about 13.8 MPa), 3000 psi (about 20.7 MPa),4000 psi (about 27.6 MPa), 5000 psi (about 34.5 MPa), 6000 psi (about41.4 MPa), 7000 psi (about 48.3 MPa), 8000 psi (about 55.2 MPa), 9000psi (about 62.1 MPa) or 10,000 psi (about 68.9 MPa). In certainembodiments, the material (e.g., polymeric material) comprising the bodyof the device or the biodegradable copolymer or polymer has a tensilestrength of at least about 3000 psi or 5000 psi. In additionalembodiments, the material (e.g., polymeric material) comprising the bodyof the device or the biodegradable copolymer or polymer has a tensilestrength of about 1000 psi to about 3000 psi, or about 3000 psi to about5000 psi, or about 5000 psi to about 10,000 psi.

In certain embodiments, the material (e.g., polymeric material)comprising the body of the device or the biodegradable copolymer orpolymer has a weight-average molecular weight (M_(W)) of at least about60,000 daltons (60 kDa), 90 kDa, 120 kDa, 150 kDa, 180 kDa, 210 kDa, or240 kDa, or 500 kDa, or 750 kDa, or 1000 kDa. In an embodiment, thematerial (e.g., polymeric material) comprising the body of the device orthe biodegradable copolymer or polymer has an M_(W) of at least about120 kDa. In further embodiments, the material (e.g., polymeric material)comprising the body of the device or the biodegradable copolymer orpolymer has an M_(W) of about 60 kDa to about 900 kDa, or about 90 kDato about 600 kDa, or about 120 kDa to about 400 kDa, or about 150 kDa toabout 250 kDa, or about 80 kDa to about 250 kDa. In an embodiment, thematerial (e.g., polymeric material) comprising the body of the device orthe biodegradable copolymer or polymer has a M_(W) of about 120 kDa toabout 250 kDa; before treatment, or after treatment, or the stentprosthesis.

In some embodiments, the material (e.g., polymeric material) comprisingthe body of the device or the biodegradable copolymer has a percentelongation at break, or at yield, or at failure of at least about 20%,50%, 70%, 100%, 150%, 200%, 250%, 300%, 400%, 500% or 600%. In certainembodiments, the material (e.g., polymeric material) comprising the bodyof the device or the biodegradable copolymer or polymer has a %elongation at yield or break or failure of about 20% to about 600%, orabout 20% to about 300%, or about 50% to about 500%, or about 50% toabout 400%, or about 50% to about 300%, or about 100% to about 400%, orabout 100% to about 300%, or about 70% to about 250%, or about 100% toabout 250%, or about 100% to about 200%. In an embodiment, the material(e.g., polymeric material) comprising the body of the device or thebiodegradable copolymer or polymer has a % elongation at break or yieldor failure of about 20% to about 300%. In a further embodiment, thematerial (e.g., polymeric material) comprising the body of the device orthe biodegradable copolymer has a tensile strength of at least about3000 psi or 5000 psi, and a % elongation at break or failure or yield ofabout 20% to about 300%.

Ductility of a polymeric material can be increased by increasing themolecular weight and decreasing the % crystallinity of the polymericmaterial. A polymeric material of higher molecular weight can also haveincreased strength (e.g., tensile strength and/or radial strength).

In one embodiment, yield strength for the biodegradable polymeric stentmaterial is at least 50% of ultimate strength, preferably at least 75%of ultimate strength, more preferably at least 90% of ultimate strength,in water at 37° C.

In one embodiment, the elastic modulus for the biodegradable metallicstent material is at least 50 GPa, preferably at least 100 GPa, morepreferably at least 150 GPa.

In another embodiment, the elastic modulus for the biodegradablepolymeric stent material is at least 0.5 GPa, preferably at least 0.75GPa, more preferably at least 1 GPa, in water at 37° C.

In one embodiment, the yield strain for the biodegradable polymericstent material is at most 10%, preferably at most 5%, more preferably atmost 3%, in water at 37° C.

In one embodiment, the plastic strain for the biodegradable polymericstent material is at least 20%, preferably at least 30%, more preferablyat least 40%, in water at 37° C.

In one embodiment, the elastic recovery of the strained biodegradablepolymeric stent material is at most 15%, preferably at most 10%, morepreferably at most 5%, in water at 37° C.

In one embodiment, the expanded biodegradable stent in physiologicalconditions at least after 1 month retains at least 25%, preferably atleast 40%, more preferably at least 70% of the strength or recoil.

The strength and/or crystallinity (e.g., degree of crystallinity) of thematerial (e.g., polymeric material) comprising the body of anendoprosthesis (e.g., a stent) can be increased by inducing orincreasing orientation of crystals, crystalline regions or polymerchains of the polymeric material substantially in the radial(circumferential) direction and/or the longitudinal direction. Strengthand/or crystallinity in the longitudinal direction can be increased byorienting crystals, crystalline regions or polymer chains substantiallyin the longitudinal direction, and strength and/or crystallinity in thecircumferential direction can be increased by orienting crystals,crystalline regions or polymer chains substantially in thecircumferential direction or substantially in a biaxial direction(neither preferentially circumferential nor preferentiallylongitudinal). Orientation of crystals, crystalline regions or polymerchains substantially in the longitudinal direction, the circumferentialdirection or a biaxial direction can be induced or increased by any ofvarious methods, such as longitudinally extending, drawing, radiallyexpanding, blow molding, pressurizing, heating or a combination thereof(performed simultaneously or sequentially), any of which can optionallybe performed under vacuum. Such method(s) can be performed at anysuitable stage of the process for fabricating the endoprosthesis, e.g.,before the polymeric article or tube is formed (e.g., heating and/ordrawing of the polymeric material by extrusion), when the polymericarticle or tube is being formed, after the polymeric article or tube isformed (e.g., heating, pressurizing, longitudinally extending and/orradially expanding the tube), and/or after the endoprosthesis is formed(e.g., heating, pressurizing, longitudinally extending and/or radiallyexpanding the endoprosthesis). In certain embodiments, orientation ofcrystals, crystalline regions or polymer chains is induced or increasedsubstantially in a direction (e.g., longitudinal, circumferential orother direction) by expanding the polymeric article and/or theendoprosthesis in that direction while the polymeric article and/or theendoprosthesis is heated at elevated temperature, e.g., at or above theT_(g) of the material (e.g., polymeric material) comprising thepolymeric article and/or the endoprosthesis, and cooling the expandedpolymeric article and/or endoprosthesis to a lower temperature (e.g.,below T_(g)).

In further embodiments, the first biodegradable polymer or material(e.g., polymeric material) comprising the polymeric article or the bodyof the device is, or has crystals, crystalline regions or polymer chainsthat are, substantially uniaxially oriented, circumferentially orientedor longitudinally oriented. In yet further embodiments, the firstbiodegradable polymer or the material (e.g., polymeric material)comprising the polymeric article or the body of the device is, or hascrystals, crystalline regions or polymer chains that are, substantiallybiaxially oriented (neither preferentially circumferentially orientednor preferentially longitudinally oriented). In other embodiments, thefirst biodegradable polymer or the material (e.g., polymeric material)comprising the polymeric article or the body of the device is, or hascrystals, crystalline regions or polymer chains that are, substantiallynot uniaxially oriented, circumferentially oriented, longitudinallyoriented or biaxially oriented. In certain embodiments, the firstbiodegradable polymer or the material (e.g., polymeric material)comprising the polymeric article or the body of the device is, or hascrystals, crystalline regions or polymer chains that are, substantiallyrandomly oriented.

In some embodiments, the biodegradable polymeric stent material can havevarying molecular architecture such as linear, branched, crosslinked,hyperbranched or dendritic.

In some embodiments, the biodegradable polymeric stent material in theinvention can range from 10 kDa to 10,000 kDa in molecular weight,preferably from 100 kDa to 1000 kDa, more preferably 300 kDa to 600 kDa.

Further embodiments of the disclosure relate to a biodegradableimplantable device comprising a body comprised of a material whichcomprises a biodegradable polylactide copolymer, wherein the materialcomprising the body or the polylactide copolymer is, or has crystals,crystalline regions or polymer chains that are, substantially notuniaxially oriented, circumferentially oriented, longitudinally orientedor biaxially oriented. In certain embodiments, the material comprisingthe body of the device or the polylactide copolymer is, or has crystals,crystalline regions or polymer chains that are, substantially randomlyoriented.

In some embodiments, the material (e.g., polymeric material) comprisingthe body of the device or the biodegradable polymer or copolymer hassmall-size or relatively small-size crystals or crystalline regions, ora large number or a relatively large number of small-size or relativelysmall-size crystals or crystalline regions. In certain embodiments, thematerial (e.g., polymeric material) comprising the body of the device orthe biodegradable copolymer or polymer is substantially randomlycrystalline, or has substantially randomly distributed crystals orcrystalline regions.

In further embodiments, the material (e.g., polymeric material)comprising the body of the device or the biodegradable copolymer orpolymer is, or has crystals, crystalline regions or polymer chains thatare, substantially not uniaxially oriented, circumferentially oriented,longitudinally oriented or biaxially oriented. In certain embodiments,the material (e.g., polymeric material) comprising the body of thedevice or the biodegradable copolymer is, or has crystals, crystallineregions or polymer chains that are, substantially randomly oriented. Instill further embodiments, the material (e.g., polymeric material)comprising the body of the device or the biodegradable copolymer orpolymer has substantially no preferred orientation or substantially nointernal texture, or has crystals, crystalline regions or polymer chainsthat have substantially no preferred orientation or substantially nointernal texture. In additional embodiments, the material (e.g.,polymeric material) comprising the body of the device or thebiodegradable copolymer or polymer is, or has crystals, crystallineregions, molecular architecture, structural order or polymer chains thatare, substantially not oriented in a particular direction, uniaxiallyoriented, circumferentially oriented, longitudinally oriented orbiaxially oriented, in certain embodiments as a result of pressurizingor expanding in a direction a polymeric article or the device comprisedof the material or the biodegradable copolymer or polymer.

In additional embodiments, the material (e.g., polymeric material)comprising the body of the device or the biodegradable copolymer orpolymer has a number-average molecular weight (M_(N)) of at least about20 kDa, 30 kDa, 40 kDa, 50 kDa, 60 kDa, 70 kDa or 80 kDa. In anembodiment, the material (e.g., polymeric material) comprising the bodyof the device or the biodegradable copolymer or polymer has an M_(N) ofat least about 40 kDa.

In further embodiments, the material (e.g., polymeric material)comprising the body of the device or the biodegradable copolymer orpolymer has an M_(W) of at least about 60 kDa, 90 kDa, 120 kDa, 150 kDa,180 kDa, 210 kDa or 240 kDa, and/or an M_(N) of at least about 20 kDa,30 kDa, 40 kDa, 50 kDa, 60 kDa, 70 kDa or 80 kDa, after the implantabledevice is exposed to radiation (e.g., ionizing radiation, such as e-beamor gamma radiation), or after exposure to heat and/or humiditytreatment. In certain embodiments, the material (e.g., polymericmaterial) comprising the body of the device or the biodegradablecopolymer or polymer has an M_(W) of at least about 120 kDa or an M_(N)of at least about 40 kDa, or both, after the device is exposed toradiation, or after exposure to heat/and or humidity treatment. In someembodiments, the material (e.g., polymeric material) comprising the bodyof the device or the biodegradable copolymer or polymer has an M_(W) ofabout 120 kDa to about 250 kDa after the device is exposed to radiation,or after the device is exposed to heat and/or humidity treatment.

In some embodiments, the material (e.g., polymeric material) comprisingthe body of the device or the biodegradable copolymer or polymer has apolydispersity of about 5 or less, or about 4 or less, or about 3 orless, or about 2.5 or less, or about 2 or less, or about 1.5 or less, orabout 1. In an embodiment, the material (e.g., polymeric material)comprising the body of the device or the biodegradable copolymer has apolydispersity of about 3 or less. A polymeric material of substantiallylow polydispersity can be prepared by any of various methods, such asionic polymerization, living polymerization, column separation, columnchromatography, size separation or gel-permeation chromatography, or acombination thereof.

In some embodiments, the material (e.g., polymeric material) comprisingthe body of the device or the biodegradable copolymer or polymer has anintrinsic viscosity of at least about 0.1 dl/g, or about 0.5 dl/g, or atleast about 1 dl/g, or at least about 1.5 dl/g, or at least about 2dl/g, or at least about 2.5 dl/g, or at least about 3 dl/g; optionallyafter the device is exposed to radiation (e.g., ionizing radiation, suchas electron beam (e-beam) radiation or gamma radiation). In certainembodiments, the material (e.g., polymeric material) comprising the bodyof the device or the biodegradable copolymer or polymer has an inherentviscosity or an intrinsic viscosity of at least about 0.5 or at least 1dl/g; optionally after the device is exposed to radiation. In additionalembodiments, the material (e.g., polymeric material) comprising the bodyof the device or the biodegradable copolymer or polymer has a relativeviscosity of at least about 0.2 dl/g, or at least about 0.5 dl/g, or atleast about 1 dl/g, optionally after the device is exposed to radiation.

The biodegradable polymeric material comprising the body of anendoprosthesis (e.g., a stent), and the biodegradable polymeric materialcomprising any coating on the endoprosthesis, can have any suitablemolecular architecture, such as linear, branched, hyperbranched,dendritic or crosslinked. The molecular weight (e.g., weight-averagemolecular weight or number-average molecular weight) of the polymericmaterial(s) can be about 10 kDa to about 10,000 kDa, or about 50 kDa toabout 5000 kDa, or about 100 kDa to about 1000 kDa, or about 100 kDa toabout 500 kDa, or about 100 kDa to about 300 kDa, or about 300 kDa toabout 600 kDa. In certain embodiments, the weight-average molecularweight of the polymeric material comprising the body of theendoprosthesis (e.g., stent), or the polymeric material comprising acoating on the endoprosthesis, is about 100 kDa to about 500 kDa.

In one embodiment, controlling the orientation of the polymeric materialachieves the desired crystallinity, or Tg. In another embodiment, thepolymeric material orientation is controlled such that the stent iscapable to be crimped from an expanded condition to a crimped condition.In another embodiment, the polymeric material orientation is controlledsuch that the stent is capable to be expanded to a deployed diameterfrom a crimped configuration. In another embodiment, the polymericmaterial orientation is controlled such that the stent is capable to beexpanded from a crimped configuration to a deployed configurationwithout fracture. In another embodiment, the polymeric materialorientation is controlled such that the material has sufficient strengthto support a body lumen. In a preferred embodiment, the polymericmaterial orientation is controlled by pressurizing the polymericmaterial with a medium such as gas such as CO₂ wherein the orientationcontrol affects crystallinity to a range from 1% to 35%, or 1% to 45%,or 1% to 55%.

Orientation of a material (e.g., polymeric material), or crystals,crystalline regions or polymer chains in the material, can bedetermined, measured or analyzed by any technique known in the art,including without limitation X-ray diffraction, see, e.g., D. Breiby andE. Samuelsen, J. Polymer Science Part B: Polymer Physics, 41:2375-2393(2003), X-ray diffraction using a texture goniometer, see, e.g., O.Engler and V. Randle, Introduction to Texture Analysis: Macrotexture,Microtexture, and Orientation Mapping, 2nd Ed., CRC Press, Boca Raton,Fla. (2010), near edge X-ray absorption fine structure (NEXAFS)spectroscopy, see, e.g., J. Stöhr, NEXAFS Spectroscopy, Springer-Verlag,Berlin (1992), scanning transmission X-ray microscopy (STXM), see, e.g.,D. Cruz et al., Biomacromolecules, 7:836-843 (2006), electronbackscatter diffraction (EBSD) using a scanning electron microscope(see, e.g., Engler and Randle, supra), transmission electron microscopy(TEM), see, e.g., A. Donald and A. Windle, J. Materials Science,18:1143-1150 (1983), and Fourier transform-infrared (FT-IR) transmissionspectroscopy and IR dichroism, see, e.g., G. Lamberti and V. Brucato, J.Polymer Science Part B: Polymer Physics, 41:998-1008 (2003).

In addition to a biodegradable polymeric material, the polymeric article(e.g., tubular body) can comprise or be comprised of a non-degradablepolymeric material, a metallic material, other material describedherein, or a combination thereof. The polymeric article can be made byany suitable method, such as spraying, dipping, extrusion, molding,injection molding, compression molding or 3-D printing, or a combinationthereof. In some embodiments, the polymeric article (e.g., a polymerictube) is made by spraying a solution or mixture of a biodegradablepolymer dissolved or dispersed in a solvent onto a structure (e.g., acylindrical structure such as a mandrel). An additional biodegradablepolymer, a non-degradable polymer, a drug or an additive (e.g., astrength-enhancing material), or a combination thereof, can optionallybe mixed with the polymer in the solvent so that the additionalmaterial(s) are incorporated in the polymeric article. Before or afterthe endoprosthesis is formed from the polymeric article, one or morecoatings containing a biodegradable polymer, a non-degradable polymer, adrug or an additive, or a combination thereof, can be applied to asurface of the polymeric article or to a surface of the endoprosthesis.

Additives can be added to the endoprosthesis to affect strength, recoil,or degradation rate, or combinations thereof. Additives can also affectprocessing of biodegradable stent material, radiopacity or surfaceroughness or others. Additives can be biodegradable ornon-biodegradable. The additives can be incorporated in to thebiodegradable stent or polymer material by blending, extrusion,injection molding, coating, surface treatment, chemical treatment,mechanical treatment, stamping, or others or combinations thereof. Theadditives can be chemically modified prior to incorporation in to thebiodegradable stent material.

In one embodiment, the percentage in weight of the additives can rangefrom 0.01% to 25%, preferably 0.1% to 10%, more preferably 1% to 5%.

In one embodiment, the additive includes at least nanoclay, nanotubes,nanoparticles, exfoliates, fibers, whiskers, platelets, nanopowders,fullerenes, nanosperes, zeolites, polymers or others or combinationthereof.

Examples of nanoclay includes Montmorillonite, Smectites, Talc, orplatelet-shaped particles, modified clay or others or combinationthereof. Clays can be intercalated or exfoliated. Example of claysinclude Cloisite NA, 93A, 30B, 25A, 15A, 10A or others or combinationthereof.

Examples of fibers include cellulose fibers such as Linen, cotton,rayon, acetate; proteins fibers such as wool or silk; plant fiber; glassfiber; carbon fiber; metallic fibers; ceramic fibers; absorbable fiberssuch as polyglycolic acid, polylactic acid, polyglyconate or others.

Examples of whiskers include hydroxyapatite whiskers, tricalciumphosphate whiskers or others.

In another embodiment, the additives includes at least modified starch,soybean, hyaluronic acid, hydroxyapatite, tricarbonate phosphate,anionic and cationic surfactants such as sodium docecyl sulphate,triethylene benzylammonium chloride, pro-degradant such as D2W (fromSymphony Plastic Technologies), photodegradative additives such as UV-H(from Willow Ridge Plastics), oxidative additives such as PDQ (fromWillow Ridge Plastics), TDPA, family of polylactic acid and its randomor block copolymers or others.

In another embodiment, the additives include electroactive orelectrolyte polymers, hydroscopic polymers, dessicants, or others.

In one embodiment, the additive is an oxidizer such an acids,perchlorates, nitrates, permanganates, salts or other or combinationthereof.

In one embodiment, the additive is a monomer of the biodegradablepolymeric stent material. For example glycolic acid is an additive topolyglycolic acid or its copolymer stent material.

In one embodiment, the additive can be water repellent monomers,oligomers or polymers such as bees wax, low MW polyethylene or others.

In another embodiment, the additive can be water attractant monomers,oligomers or polymers such as polyvinyl alcohol, polyethylene oxide,glycerol, caffeine, lidocaine or other.

In one embodiment, the additive can affect crystallinity of thebiodegradable polymeric stent material. Example of additive of nanoclayto PLLA affects its crystallinity.

In further embodiments, the body of the device, or the materialcomprising the body of the device, or the material comprising one ormore layers of the body of the device, comprises one or more additives.The additive(s) can serve any of a variety of functions, includingwithout limitation facilitating processing of the material comprisingthe body (or the material comprising any coating on the body), impartingsurface roughness to a surface of a polymer layer in the body or on thebody (e.g., to improve adhesion of a metal layer to the polymer layer inthe body or on the body of the device), imparting radiopacity to thedevice, and controlling physical characteristics of the materialcomprising the body (or the material comprising any coating on thebody), such as controlling (e.g., promoting or slowing down) itsdegradation and/or controlling its crystallinity, enhancing itsstrength, and enhancing its toughness. The additive(s) can bebiodegradable or non-degradable. The additive(s) can be incorporated inand/or on the body (and in and/or on any coating on the body of thedevice) by any suitable method, such as mixing, blending, spraying,dipping, extrusion, injection molding, coating, printing, surfacetreatment, chemical treatment, mechanical treatment, stamping, or acombination thereof.

In some embodiments, the weight percent of an additive in the material(e.g., polymeric material) comprising the body of the device, or thematerial (e.g., polymeric material) comprising a particular layer in thebody, or the material (e.g., polymeric material) comprising a particularcoating on the body, is about 0.01% or 0.1% to about 50%, or about 0.01%or 0.1% to about 40%, or about 0.01% or 0.1% to about 30%, or about0.01% or 0.1% to about 25%, or about 0.05% or 0.1% to about 20%, orabout 0.05% or 0.1% to about 15%, or about 0.1% to about 10% or 20%, orabout 0.5% to about 10% or 20%, or about 1% to about 10% or 20%, orabout 0.5% or 1% to about 5%. In certain embodiments, the weight percentof an additive in the material (e.g., polymeric material) comprising thebody of the device, or the material (e.g., polymeric material)comprising a particular layer in the body, or the material (e.g.,polymeric material) comprising a particular coating on the body, isabout 0.1% to about 25%.

Non-limiting examples of additives include nanotubes, carbon nanotubes,carbon nano fibers, boron nanotubes, fullerenes, nanoparticles,nanospheres, nanopowders, nanoclays, zeolites, exfoliates, fibers,whiskers, platelets, polymers, monomers, oxidizers, stabilizers,antioxidants, butylated hydroxytoluene (BHT), degradation-controllingagents, buffers, conjugate bases, weak bases, getters, ionicsurfactants, salts, barium salts, barium sulfate, calcium salts, calciumcarbonate, calcium chloride, calcium hydroxyapatite, tricalciumphosphate, magnesium salts, sodium salts, sodium chloride, blowingagents, gases, carbon dioxide, solvents, methanol, ethanol, isopropanol,dichloromethane, dimethylsulfoxide, metals, metal alloys, semi-metals,ceramics, radiopaque agents, and contrast agents.

Examples of nanoclays include, but are not limited to, montmorillonites,smectites, bentonites, talc, particles have any desired shape (e.g.,platelet-shaped particles), and modified clays. Additional examples ofnanoclays include Cloisite® NA, 10A, 15A, 25A, 30B and 93A. Nanoclayscan be, e.g., intercalated or exfoliated, and can serve any of a varietyof functions, such as controlling crystallinity of the material (e.g.,polymeric material) comprising the body of the device or a coating onthe body, e.g., a nanoclay as an additive can affect crystallinity ofpoly(L-lactide).

Examples of fibers include without limitation plant fibers and cellulosefibers (e.g., linen, cotton, rayon and cellulose acetate), proteinsfibers (e.g., wool and silk), glass fibers, carbon fibers, metallicfibers, ceramic fibers, and absorbable polymeric fibers (e.g.,polyglycolic acid/polyglycolide, polylactic acid/polylactide,poly(lactide-co-ε-caprolactone), and polyglyconate). Examples ofwhiskers include, but are not limited to, hydroxyapatite whiskers andtricalcium phosphate whiskers.

The additives can be a blowing agent, which is a substance capable ofproducing a cellular structure in a variety of materials that undergohardening or phase transition, such as polymers, plastics and metals.The blowing agent can be applied when the material is in a liquid stageor in a liquid solution or mixture. Blowing agents include withoutlimitation gases (e.g., compressed gases) that expand when pressure isreleased, solids (e.g., soluble solids) that form pores when they leachout from the material, liquids that develop a cellular structure (e.g.,cells) when they change to gases, and chemical agents that decompose orreact under the influence of heat or radiation to form, e.g., a gas or asolid that can form pores when it leaches out. Chemical blowing agentsinclude, but are not limited to, salts (e.g., ammonium and sodium salts,such as ammonium and sodium bicarbonate) and nitrogen-releasing agents.

Examples of radiopaque agents and material that can be additives includewithout limitation barium sulfate, gold, magnesium, platinum,platinum-iridium alloys (e.g., those containing at least about 1%, 5%,10%, 20% or 30% iridium), tantalum, tungsten, and alloys thereof. Theradiopaque agent or material can be in any suitable form (e.g.,nanoparticle or microparticle), and in amounts ranging from about 0.1%to about 10%.

Contrast agents include without limitation radiocontrast agents and MRIcontrast agents. Non-limiting examples of radiocontrast agents includeiodine-based agents, ionic iodine-based agents, diatrizoate, ioxaglate,metrizoate, non-ionic (organic) iodine-based agents, iodixanol, iohexol,iopamidol, iopromide, ioversol, ioxilan, barium-based agents, and bariumsulfate. Non-limiting examples of MRI contrast agents includegadolinium-based agents, gadobenic acid, gadobutrol, gadocoletic acid,gadodenterate, gadodiamide, gadofosveset, gadomelitol, gadopenamide,gadopentetic acid, gadoteric acid, gadoteridol, gadoversetamide,gadoxetic acid, iron oxide-based agents, Cliavist, Combidex®, Endorem(Feridex), Resovist®, Sinerem, manganese-based agents, and mangafodipir(Mn(II)-dipyridoxyl diphosphate).

The additives can also be selected from modified starch, soybean,hyaluronic acid, hydroxyapatite, tricarbonate phosphate, TotallyDegradable Plastic Additive (TDPA™), desiccants (e.g., calcium sulfate,calcium chloride, activated alumina, silica gel, montmorillonites,zeolites and molecular sieves), anionic and cationic surfactants (e.g.,sodium dodecyl sulphate and triethylene benzylammonium chloride),pro-degradant additives (e.g., D2W from Symphony Plastic Technologies),photodegradative additives (e.g., UV-H from Willow Ridge Plastics),oxidative additives (e.g., PDQ from Willow Ridge Plastics), andoxidizers (e.g., acids, salts, perchlorates, nitrates andpermanganates).

Furthermore, the additives can be selected from electroactive polymers,electrolyte polymers, hygroscopic polymers, and hydrophilic polymers(e.g., polylactic acid/polylactide and polyglycolic acid/polyglycolideand copolymers thereof). The additives can also be monomers of thepolymeric material comprising the body of the device (or the polymericmaterial comprising a coating on the body). For example, glycolic acidor glycolide is an additive for a polymer containing glycolicacid/glycolide, e.g., polyglycolic acid/polyglycolide or a copolymerthereof, such as poly(lactide-co-glycolide), lactic acid or lactide isan additive for a polymer containing lactic acid/lactide, e.g.,polylactic acid/polylactide or a copolymer thereof, such aspoly(lactide-co-glycolide), and ε-caprolactone is an additive for apolymer containing ε-caprolactone, e.g., poly(ε-caprolactone) or acopolymer thereof, such as poly(lactide-co-ε-caprolactone). Additivesthat are monomers can serve any of a variety of functions, such ascontrolling degradation of the material (e.g., polymeric material)comprising the body of the device or a coating on the body (e.g., acidicmonomers such as glycolic acid and lactic acid can promote degradationof the polymeric material), or plasticizing or softening the polymericmaterial, which can, e.g., reduce its crystallinity or brittleness andenhance its toughness. In other embodiments, monomers of a differenttype than copolymers or polymers can be used.

In some embodiments, the additives are degradation-controlling agentsthat control degradation of the material (e.g., polymeric material)comprising the body of the device or a coating on the body, or thatcontrol degradation of any portion of the device. Non-limiting examplesof degradation-controlling agents include salts (e.g., aluminumchloride, calcium chloride, ferric chloride, magnesium chloride, sodiumchloride and zinc chloride), acids (e.g., ammonium chloride,aminosulfonic acid, hydrochloric acid, hydrofluoric acid, nitric acid,phosphoric acid, sulfuric acid, hexafluorosilicic acid, sodiumbisulfite, acetic acid, adipic acid, hydroxyadipic acids, citric acid,formic acid, lactic acid and oxalic acid), bases (e.g., potassiumhydroxide, sodium hydroxide, calcium carbonate, potassium carbonate,sodium carbonate, potassium bicarbonate, sodium bicarbonate, phosphates,potassium phosphate, sodium phosphate, hydroxyapatites and calciumhydroxyapatite), natural and unnatural amino acids (e.g., the 20 naturalamino acids in the human body), polymers with acidic or basic byproduct(e.g., polylactide and copolymers thereof, and polyglycolide andcopolymers thereof), blowing agents (e.g., bromine, chlorine, nitrogen,oxygen, carbon dioxide, nitrogen-releasing agents, and ammonium andsodium salts, such as ammonium and sodium bicarbonate), and metals andmetal alloys (e.g., metals and metal alloys that comprise calcium,chromium, lithium, magnesium, potassium, silicon, a silicate or sodium,or a combination thereof). Additional examples ofdegradation-controlling agents are described herein and in U.S. patentapplication Ser. No. 11/398,363, the full disclosure of which isincorporated herein by reference.

In certain embodiments, the additives are degradation-controlling agentsthat promote degradation of a non-degradable polymer. For example,pro-degradant additives such as D2W, photodegradative additives such asUV-H, oxidative additives such as PDQ, and Totally Degradable PlasticAdditive (TDPA™) can promote degradation of non-degradable polymers suchas polyethylene, polypropylene and poly(ethylene terephthalate).

In other embodiments, the additives are degradation-controlling agentsthat help to resist degradation of a material (e.g., a polymer, a metalor metal alloy, a biologically active agent, or another additive), suchas oxidative degradation, photodegradation, high energy-exposuredegradation, thermal degradation, hydrolytic degradation, acid-catalyzeddegradation, or other kinds of degradation. Non-limiting examples ofadditives that can help to resist degradation of a material includeantioxidants, e.g., vitamin C and butylated hydroxy toluene (BHT),stabilizers (e.g., xanthum gum, succinoglycan, carrageenan and propyleneglycol alginate), getters (e.g., titanium-containing beads and aluminiumoxide), salts (e.g., calcium chloride), and bases (e.g., potassiumcarbonate, sodium carbonate, potassium bicarbonate, sodium bicarbonate,sodium sulfate and magnesium sulfate).

In addition, the additives can be water-attractant substances such asglycerol, caffeine, lidocaine, monomers, oligomers or polymers (e.g.,polyvinyl alcohol or polyethylene oxide). The additives can also bewater-repellent substances such as monomers, oligomers, polymers (e.g.,low molecular weight polyethylene) or waxy substances (e.g., beeswax).Water-attractant additives can serve any of a variety of functions,including promoting degradation of the material (e.g., polymericmaterial) comprising the body of the device or a coating on the body andpermeation of water into the polymeric material, which can swell thepolymeric material, reduce its brittleness and increase its toughness.Water-repellent additives can serve any of a variety of functions,including slowing down degradation of the material (e.g., polymericmaterial) comprising the body of the device or a coating on the body.

In certain embodiments, the additives are additives that reduce waterabsorption, act as a water barrier or react with water (designed, e.g.,to control degradation of the device, control elasticity or ductility ofa polymeric material comprising the device, or control self-expansion ofa self-expandable device in aqueous condition at about 37° C.). Forexample, the additives can be metals or metal alloys that react withwater, such as magnesium, magnesium alloys, iron or iron alloys. Asanother non-limiting example, the additives can be salts that react withwater, such as calcium salts, magnesium salts or sodium salts.

Additives that might be non-degradable can be removed by a variety ofmeans, such as by cells (e.g., macrophages and monocytes) or byexcretion (e.g., when they are not used in a large amount).

In certain embodiments, the material (e.g., polymeric material)comprising the body of the device, or the material (e.g., polymericmaterial) comprising a particular layer of the body, comprises novolimusand an antioxidant. In an embodiment, the antioxidant is butylatedhydroxytoluene (BHT). In some embodiments, the weight percent of theantioxidant in the novolimus-containing material is about 0.1% to about2%, or about 0.1% to about 1%, or about 0.5% to about 1%. In certainembodiments, the material (e.g., polymeric material) comprising the bodyof the device or any particular layer or all layers of the bodycomprises novolimus and BHT, wherein the weight percent of the BHT inthe material is about 0.1% to about 1%.

In some embodiments, the biodegradable implantable devices describedherein comprise one or more reinforcement additives. The reinforcementadditives can improve properties of the devices, such as strength (e.g.,tensile strength, radial strength) and modulus (e.g., elastic modulus,tensile modulus). Further, the additives can increase retention orcontrol release of a biologically active agent, e.g., as a result ofphysical interaction, non-covalent interaction (e.g., van der Waalsinteraction or hydrogen bonding), and/or covalent interaction (e.g., ifthe additives are functionalized) between the additive and the bioactiveagent.

Non-limiting examples of reinforcement additives include nanotubes(including carbon nanotubes/nanofibers and boron nanotubes/nanofibers),fullerenes (including buckyballs), nanoparticles, nanospheres,nanopowders, nanoclays, zeolites, exfoliates, fibers (includingnanofibers), whiskers, platelets and polymers. Nanoclays can be added toone or more polymers comprising the body of the device or a coating onthe device by any suitable method, such as in situ polymerizationintercalation, melt intercalation and solution intercalation. In certainembodiments, the reinforcement additives incorporated in the body of thedevice, a layer of the body or a coating on the device include carbonnanotubes. In further embodiments, the device comprising one or morereinforcement additives is a stent.

In some embodiments, the weight percent of a reinforcement additive inthe material (e.g., polymeric material) comprising the body of thedevice, or the material (e.g., polymeric material) comprising a layer ofthe body, or the material (e.g., polymeric material) comprising acoating on the device, is about 0.01% or 0.1% to about 25%, or about0.1% to about 15% or 20%, or about 0.1% or 0.25% to about 10%, or about0.25% or 0.5% to about 5%, or about 1% to about 5%. In certainembodiments, the weight percent of a reinforcement additive is about0.5% to about 5%, or about 1% to about 3%. In further embodiments, thevolume fraction or volume percent of a reinforcement additive in thebody of the device, a layer of the body or a coating on the device isabout 0.05% or 0.1% to about 25%, or about 0.25% or 0.5% to about 10%,or about 0.75% or 1% to about 5%. In certain embodiments, the volumefraction or volume percent of a reinforcement additive is about 0.75% toabout 5%, or about 1% to about 3%.

In certain embodiments, the material (e.g., polymeric material)comprising the body of the device, or the material (e.g., polymericmaterial) comprising a particular layer of the body, comprises nanotubes(e.g., carbon nanotubes, boron nanotubes) or one or more otherreinforcement additives having a larger feature (e.g., length) and asmaller feature (e.g., diameter or width) such that the ratio of thesetwo features results in a relatively high aspect ratio. In someembodiments, the average aspect ratio (e.g., length divided by diameteror width) of a reinforcement additive is about 2 to about 40,000, orabout 10 or 30 to about 25,000, or about 100 to about 1000, 5000 or10,000, or about 50 or 100 to about 500.

Incorporation of one or more reinforcement additives having a relativelyhigh aspect ratio in the material comprising the body of the device or alayer of the body (e.g., by mixing or dispersing the additives in one ormore polymers comprising the body or a layer of the body) can improveproperties of the device. For example, use of such reinforcementadditives can increase the strength (e.g., tensile strength, radialstrength), stiffness, modulus (e.g., tensile modulus, elastic modulus),toughness, crack resistance, fatigue resistance, work to failure, and/orthermal conductivity of the device (e.g., a stent), and can decreasecracking, fatigue, creep and/or recoil of the device.

In some embodiments, the material (e.g., polymeric material) comprisingthe body of the device, or the material (e.g., polymeric material)comprising a particular layer of the body, comprises carbon nanotubes.Carbon nanotubes can be strong and flexible, and can enhance propertiesof the material, such as increasing its strength (e.g., tensilestrength, radial strength) and/or modulus (e.g., elastic modulus,tensile modulus) without substantially decreasing its ductility. Incertain embodiments, the device comprising carbon nanotubes is a stent.

The carbon nanotubes (CNTs) can be single-walled carbon nanotubes(SWCNTs), double-walled carbon nanotubes (DWCNTs), and/or multi-walledcarbon nanotubes (MWCNTs). In certain embodiments, the number of wallsof MWCNTs is about 2 to about 5, 10, 15 or 20. In an embodiment, thenumber of walls of MWCNTs is about 2 to about 4. MWCNTs can potentiallybe straighter and/or more crystalline than SWCNTs, and can potentiallyprovide higher mechanical properties than SWCNTs. SWCNTs can comprise agraphene sheet rolled into a cylinder, and MWCNTs can comprise multipleconcentric graphene cylinders. Carbon nanotubes can be produced by anysuitable method, such as high-temperature evaporation using arcdischarge, laser ablation, chemical vapor deposition, high-pressurecarbon monoxide, or a catalytic growth process.

In some embodiments, the average length of the carbon nanotubes is about100 nm to about 50 or 100 mm, or about 500 nm to about 0.5 or 1 mm, orabout 500 nm to about 50 or 100 μm, or about 1 or 5 μm to about 50 μm,or about 10 μm to about 20 μm. In certain embodiments, the averagediameter of the carbon nanotubes is about 0.4 nm to about 1 μm, or about1 nm to about 100 or 500 nm, or about 10 or 30 nm to about 50 nm. Insome embodiments, the average aspect ratio (length divided by diameter)of the carbon nanotubes is about 2 to about 40,000, or about 10 or 30 toabout 25,000, or about 100 to about 1000, 5000 or 10,000. In furtherembodiments, the average surface area of the carbon nanotubes is about10 to about 1000 m²/g, or about 25 to about 750 m²/g, or about 50 or 100to about 500 m²/g.

In additional embodiments, the purity of the carbon nanotubes is atleast about 50%, 60%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98% or 99%. Inan embodiment, the purity of the carbon nanotubes is at least about 95%.In certain embodiments, impurities of carbon nanotubes include amorphouscarbon, heavy metals and/or chemicals.

In certain embodiments, the material (e.g., polymeric material)comprising the body of the device or a particular layer of the bodycomprises carbon nanotubes in a weight percent of about 0.1% or 0.5% toabout 10%, or about 0.1% or 0.5% to about 5%, or about 0.1%, 0.5%, 1%,1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9% or 10%. In someembodiments, the material (e.g., polymeric material) comprising the bodyof the device or a particular layer of the body comprises carbonnanotubes in a weight percent of about 0.1% or 0.5% to about 3%, orabout 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5% or 3%. In further embodiments, thecarbon nanotube-containing material comprises a polylactide homopolymeror copolymer, wherein lactide includes L-lactide, D-lactide andD,L-lactide. In certain embodiments, the material comprising the body ofthe device or a particular layer of the body comprises a poly(L-lactide)copolymer, e.g., poly(L-lactide-co-ε-caprolactone) or any otherpoly(L-lactide) copolymer described herein, and carbon nanotubes in aweight percent of about 0.1% or 0.5% to about 3%, or about 0.1%, 0.5%,1%, 1.5%, 2%, 2.5% or 3% (e.g., about 2%).

One or more reinforcement additives can be incorporated in the body ofthe device or a coating on the device in any of a variety of ways. Insome embodiments, one or more additives are mixed or dispersed in one ormore polymers comprising the body of the device, a layer of the body ora coating on the device when the polymer(s) are untangled or lack formor crystalline structure, which can promote interaction or incorporationof the additive(s) with the polymer molecules. Substantially amorphouspolymers or semi crystalline polymers or polymers of lower crystallinitycan have higher loading of additives, which can result in greaterincrease in strength and/or toughness and/or lower creep.

In some embodiments, one or more reinforcement additives are mixed ordispersed in one or more polymers comprising the body of the device, alayer of the body or a coating on the device such that the polymer(s)contact or wet the surface of the additive(s), which can help totransfer stress from the polymer(s) to the additive(s) and increase thestrength of the polymeric material. In certain embodiments, theadditive(s) are substantially completely or substantially uniformlydispersed in the polymer(s), which can prevent or minimize aggregationof the additive(s) and disperse stress.

Chemical modification of additives can prevent the additives fromaggregating, improve dispersion of the additives in solvents (e.g.,water, organic solvents), improve dispersion of the additives inpolymers, and improve interaction between the additives and polymers.For example, modification of additives can create stronger interactionbetween the additives and polymers, which can increase the strength andtoughness of the resulting material. Non-limiting examples ofmodifications of additives include acid treatment, base treatment,plasma treatment, oxidation (e.g., with oxygen), functionalization of afunctional group (e.g., an amino, hydroxyl or carboxyl group), andconjugation to a polymer, e.g., polyethylene glycol,poly(propionylethylenimine-co-ethylenimine) As an example, the surfaceof carbon nanotubes can be functionalized with carboxyl, hydroxyl,amino, amide, fluoro, alkyl, and/or other groups. Further, the surfaceof carbon nanotubes can be conjugated to poly(m-phenylenevinylene)having octyloxy chains, polyethylene glycol,poly(propionylethylenimine-co-ethyleneimine), polyethyleneimine, and/orother polymers, which can prevent aggregation of the nanotubes andimprove dispersion of the nanotubes in a solvent or a polymeric materialcomprising the body of the device or a coating on the device.

The manner in which an additive is mixed with a polymer in a solvent(which can be a mixture of solvents) can influence how uniformlydispersed in the polymer the additive is. Non-limiting examples ofsolvents that can be used to dissolve, suspend or disperse additivesinclude amide-containing solvents, dimethylformamide,N-methylpyrrolidone, ketones, acetone, ethers, tetrahydrofuran,halogenated solvents, dichloromethane, chloroform, Freon, Freonsubstitutes, monochlorobenzene, alcohols, ethanol, and methanol. Incertain embodiments, an additive is slowly added (e.g., in increments ordropwise) to a solvent that may or may not contain a polymer. To aiddissolution, suspension or dispersion of the additive in the solvent,the mixture can be stirred, shaken or vortexed. The mixture can also besubjected to a relatively high RPM mixer or centrifuge, and/or exposedto ultrasound energy (homogenizer or bath). In certain embodiments, themixture is exposed to ultrasound having a frequency no more than about45 kHz, 35 kHz, 25 KHz or 15 kHz.

An anionic, cationic or non-ionic surfactant can be used to aiddissolution, suspension or dispersion of an additive in a solvent.Non-limiting examples of such surfactants include polyvinylpyrrolidone,polystyrenesulfonate and polyallylamine hydrochloride, sodiumdodecylbenzenesulfonate, sodium lauryl sulfate, ethoxylated castor oil,polyethylene glycol, polyvinyl butyral, poly(oxy-1,2-ethanediyl), Tweensurfactants (e.g., Tween 20, Tween 60), Pluronic surfactants (e.g.,Pluronic F127, Pluronic L61, Pluronic L92), Triton surfactants (e.g.,Triton X-100, Triton X-405), Igepal surfactants (e.g., Igepal CO-720,Igepal CO-890), and derivatives and adducts thereof. In certainembodiments, the amount of a surfactant relative to the weight of anadditive is about 0.1% or 0.5% to about 20%, or about 0.1% or 0.5% toabout 10%, or about 0.5% or 1% to about 7.5%, or about 0.5% or 1% toabout 5%.

A solution or mixture containing one or more reinforcement additives andone or more polymers can be applied to a structure (e.g., asubstantially cylindrical structure, such as a mandrel) by spraying ordipping to form a polymeric article (e.g., a polymeric tube) or a layerof the polymeric article, or can be applied by spraying or dipping toform a coating on a device (e.g., a stent). Alternatively, such asolution or mixture can optionally be filtered and then can beconcentrated (e.g., by evaporation or in vacuo) to provide a materialthat can be used to form a polymeric article (e.g., a polymeric tube) byextrusion, 3-D printing or molding (e.g., injection molding orcompression molding). The polymeric article can undergo any treatmentsdescribed herein (e.g., longitudinal extension, radial expansion,heating, pressurizing, vacuuming, or exposure to radiation or carbondioxide, or a combination thereof), which can control or improvecharacteristics (e.g., crystallinity, strength, toughness,residual/internal stress, and/or degradation) of the material comprisingthe polymeric article. A device (e.g., a stent) can be formed from thepolymeric article (e.g., polymeric tube) by any suitable method (e.g.,laser cutting).

In some embodiments, one or more reinforcement additives are mixed withor dispersed in one or more polymers having an adjustable orcontrollable T_(g) in the body of the device, a layer of the body or acoating on the device. In certain embodiments, the T_(g) of a polymermixed with a reinforcement additive is substantially similar to theT_(g) of the polymer not mixed with the additive (e.g., as a result of alack of chemical interaction between the polymer and the additive).Physical interaction between a polymer and an additive can be maximized,without chemical interaction between the polymer and the additive, e.g.,by having the polymer wrap around (e.g., helically) the additive. Inother embodiments, the T_(g) of a polymer mixed with a reinforcementadditive is higher than the T_(g) of the polymer not mixed with theadditive, which can be a result of chemical interaction (e.g.,non-covalent interaction, such as van der Waals interaction or hydrogenboding) between the polymer and the additive. In yet other embodiments,the T_(g) of a polymer mixed with a reinforcement additive is lower thanthe T_(g) of the polymer not mixed with the additive, which can be aresult of a lack of chemical interaction between the polymer and theadditive and/or a lack of void or free surface between the polymer andthe additive.

In additional embodiments, one or more reinforcement additivesincorporated in the body of the device, a layer of the body or a coatingon the device are oriented in a substantially similar direction. Incertain embodiments, the additive(s) are oriented in a direction ofstress (e.g., radial direction), which can enhance the tensile modulus,stiffness and/or yield strength of the material (e.g., polymericmaterial) comprising the body of the device or a coating on the device.Orientation of the additive(s) can be promoted by electric or magneticfield before the material becomes hardened, and can be controlled bytemperature and shear stress (e.g., longitudinal or radial). Orientationof the additive(s) can also be promoted by spinning a substantiallycylindrical structure (e.g., a mandrel) in the direction of desiredorientation while applying a solution or mixture of polymer(s) and theadditive(s) onto the mandrel by spraying or dipping.

The biodegradable implantable device can be any of a wide variety ofimplantable devices, and can be implanted in a subject for treatment ofa wide variety of diseases, disorders and conditions. In someembodiments, the device substantially completely degrades within about 4years, or within about 3 years, or within about 2 years, or within about1 year, or within about 6 months in aqueous condition at about 37° C. invitro or in vivo.

In an embodiment, the device substantially completely degrades withinabout 2 years in aqueous condition at about 37° C. in vitro or in vivo.

In one embodiment, the biodegradable stent material degradessubstantially within 2 years, preferably within 1 year, more preferablywithin 9 months.

In one embodiment, the biodegradable polymeric stent materials degradesby at least bulk erosion, surface erosion, or combination thereof.

In one embodiment, the biodegradable polymeric stent material degradesby at least hydrolytic degradation, enzymatic degradation, oxidativedegradation, photo degradation, degradation under physiologicalenvironment or combination thereof.

In some embodiments, the biodegradable device described hereinsubstantially completely degrades within about 48 months, or withinabout 42 months, or within about 36 months, or within about 30 months,or within about 24 months, or within about 18 months, or within about 12months, or within about 9 months, or within about 6 months, or withinabout 3 months in aqueous condition (e.g., in aqueous solution, water,saline solution or physiological conditions) at about 37° C. in vitro orin vivo. In an embodiment, the device substantially completely degradeswithin about two years in aqueous condition (e.g., in aqueous solution,water, saline solution or physiological conditions) at about 37° C. invitro or in vivo.

In certain embodiments, the device substantially completely degradeswithin about 24 months, 18 months, 12 months, 9 months or 6 months, andthe body of the device is comprised of the biodegradable copolymer andan additional biodegradable polymer and/or a non-degradable polymer,wherein degradation of at least one of the polymers (homopolymer orcopolymer) is promoted in the presence of the other polymers. Forexample, degradation of at least one of the polymers (e.g., a lactide-,glycolide- or caprolactone-containing homopolymer or copolymer) canprovide an acidic or basic by-product (e.g., lactic acid, glycolic acidor caproic acid) that promotes degradation of at least one of the otherpolymers.

Without limiting to any mechanisms of action, it is believed thatcertain levels of inflammation are related to the pH of the degradationby products of the biodegradable devices and biodegradable polymersdescribed herein. In some embodiments, the pH of lactic acid producedfrom lactide based polymers is about 3 to about 5 and the pH of glycolicacid produced from glycolide based polymers is from about 2 to about 5.In some preferred embodiments, the pH of the by products produced fromthe degradation of the biodegradable devices and biodegradable polymersis about 2 to about pH 7 and in certain other embodiments the pH isacidic and is higher than about 5. Following in vivo implantation of theimplantable device, prosthesis, and articles described herein, thefollowing semi-quantitative scores may be obtained to determine theeffect of the device, prosthesis, or article—injury score, inflammationscore, fibrin score, endothelialization score, and neointimal immaturityscore. Such scores are obtained following examination of suitable tissuesamples under a light microscope. Such scores may be related to the aciddegradation by products of the material (e.g., polymeric material). Theinjury score is related to the laceration of the internal elasticlamina, the inflammation score is related to the amount of inflammatorycells at the implant location, fibrin score is related to the amount offibrin, endothelialization score is related to the % of arterycircumference covered by endothelium, and the neointimal immaturityscore is related to the neointimal containing hypocellular areas. Inpreferred embodiments, following implantation the implantable device,prosthesis, and articles described herein provide low or medium scoresfor the injury score, inflammation score, fibrin score,endothelialization score, and neointimal immaturity score. For example,if the scoring scheme is 0 for no inflammation and 3 for highinflammation, it is preferred to have a mean score or 0, 1, or 2, or2.5. Such inflammation scores, in some embodiments, are maintained forthe entire period of use. Also, in some embodiments, the inflammationscores are maintained at 7 day or less, or 28 day or less, or about 60day or less, or about 90 day or less.

In some embodiments, the device decreases in mass by about 50% or morewithin about 24 months, or within about 18 months, or within about 12months, or within about 9 months, or within about 6 months, or withinabout 3 months in aqueous condition (e.g., in aqueous solution, water,saline solution or physiological conditions) at about 37° C. in vitro orin vivo. In an embodiment, the device decreases in mass by about 50% ormore within about one year in aqueous condition (e.g., in aqueoussolution, water, saline solution or physiological conditions) at about37° C. in vitro or in vivo.

In additional embodiments, the average mass loss of the device, or theaverage mass loss of the material comprising the body of the device, orthe average mass loss of the material comprising a coating on thedevice, is about 0.05% per day to about 3% per day, or about 0.075% perday to about 2% per day, or about 0.1% per day to about 1% per day, orabout 0.14% per day to about 1.1% per day, or about 0.1% per day toabout 0.75% per day, or about 0.15% per day to about 0.8% per day, orabout 0.14% per day to about 0.6% per day, or about 0.2% per day toabout 0.6% per day, or about 0.25% per day to about 0.5% per day. In anembodiment, the average mass loss of the device is about 0.14% per dayto about 0.6% per day.

Degradation of the body of the device and/or a coating on the device mayoccur in multiple phases, such as a slower degradation rate in one phaseand a faster degradation rate in another phase. In some embodiments, thebody of the device and/or a coating on the device degrade at a slowerrate in an initial phase and at a faster rate in a later phase. In otherembodiments, the body of the device and/or a coating on the devicedegrade at a faster rate in an initial phase and at a slower rate in alater phase. Degradation may be uniform along or throughout the body ofthe device and/or a coating on the device, or may be variable along orthroughout the body of the device and/or a coating on the device.

Degradation of the device can be controlled by any of a variety of ways.As an example, the body of the device can be comprised of a polymer thathas a weight-average molecular weight of a certain value or in a certainrange of values. For example, using a polymer of lower weight-averagemolecular weight can result in shorter degradation time. As anotherexample, the body of the device can comprise a polymer, e.g.,poly(L-lactide-co-ε-caprolactone), and/or a coating on the device cancomprise a polymer, e.g., poly(L-lactide-co-glycolide)], that isamorphous, hydrophilic or water-permeable to promote degradation of thebody and/or the coating. As a further example, the body of the deviceand/or a coating on the device can comprise a more crystalline polymer,e.g., poly(L-lactide), that absorbs less water over time to slow downdegradation of the body and/or the coating.

As yet another example, the body of the device and/or a coating on thedevice can comprise one or more additives that promote absorption ofwater, react with water or promote hydrolysis of the material(s), e.g.,polymeric material(s), comprising the body and/or the coating, which canpromote degradation of the body and/or the coating. As a furtherexample, the body of the device and/or a coating on the device cancomprise one or more additives that reduce water absorption or act as awater barrier, which can slow down degradation of the body and/or thecoating.

Furthermore, the body of the device can comprise features in and/or onthe body, and/or a coating on the device can comprise features in and/oron the coating, which promote degradation of the body and/or thecoating. Examples of degradation-promoting features include withoutlimitation openings, pores (including partial pores and through pores),holes (including partial holes and through holes), voids, recesses,pits, cavities, trenches, reservoirs and channels. Such features canallow water to penetrate into the body and/or the coating, and/or cancollect water and any degradation by-product(s), e.g., acidic or basicby-product(s) of degradation of polymer(s), to promote degradation ofthe polymer(s) and any metal(s) or metal alloy(s) comprising the bodyand/or the coating. Additional examples of degradation-promotingfeatures include corrosion-inducing features described in U.S. patentapplication Ser. No. 11/398,363.

In some embodiments, the material (e.g., polymeric material) comprisingthe body of an endoprosthesis (e.g., a stent) substantially degradeswithin about 2 years, or within about 1.5 years, or within about 1 year,or within 9 months, or within about 6 months, or within about 3 monthsin aqueous condition (e.g., in aqueous solution, water, saline solutionor physiological conditions) at about 37° C. in vitro or in vivo.

In additional embodiments, an endoprosthesis (e.g., a stent) comprisedof a biodegradable polymeric material substantially completely degradeswithin about 4 years, or within about 3.5 years, or within about 3years, or within about 2.5 years, or within about 2 years, or withinabout 1.5 years, or within about 1 year, or within about 9 months, orwithin about 6 months, or within about 3 months in aqueous condition(e.g., in aqueous solution, water, saline solution or physiologicalconditions) at about 37° C. in vitro or in vivo. In an embodiment, theendoprosthesis (e.g., stent) substantially completely degrades withinabout two years in aqueous condition (e.g., in aqueous solution, water,saline solution or physiological conditions) at about 37° C. in vitro orin vivo.

The material (e.g., polymeric material) comprising the body of anendoprosthesis (e.g., a stent), and the material (e.g., polymericmaterial) comprising any coating on the endoprosthesis, can degrade bybulk erosion and/or surface erosion. The material(s), e.g., polymericmaterial(s), can degrade by any mechanism, such as degradation underphysiological conditions, hydrolytic degradation, enzymatic degradation,oxidative degradation, photo-degradation, or a combination thereof.

The body of the device can be formed from a polymeric material made byany suitable method, such as spraying, dipping, extrusion, molding,injection molding, compression molding, or three-dimensional (3-D)printing, or a combination thereof. In certain embodiments, the body ofthe device is formed from a polymeric article made by spraying asolution or mixture containing at least the biodegradable copolymer orpolymer and at least one solvent onto a structure. When the device is astent, a stent can be laser-cut from a polymeric tube made by sprayingthe polymer solution or mixture onto a mandrel. In another embodiment,the tubular body comprising the biodegradable polymer is patterned intoa stent using (3-D) printing or laser cut. In another embodiment, thetubular body comprising the biodegradable polymer is formed usingextrusion or spraying or dipping, or molding, and is patterned into astent. In certain embodiments, the stent or body of the device comprisesone or more additional polymer layers, and/or one or more metal or metalalloy layers, the additional polymer layer(s) of the polymeric materialcan be formed by spraying additional solution(s) or mixture(s)containing a biodegradable polymer, and/or the metal layer(s) can beformed by applying metal film(s), foil(s) or tube(s). In someembodiments, a polymer solution or mixture can contain one or moreadditional biodegradable polymers and/or one or more non-degradablepolymers, and can also contain one or more biologically active agentsand/or one or more additives. In another embodiment, the stent ortubular body comprises radiopaque markers. Radiopaque markers can bemetallic such as gold, platinum, iridium, bismuth, or combinationthereof, or alloys thereof. Radiopaque markers can also be polymericmaterial. Radiopaque markers can be incorporated in the stent or tubularbody when it is being formed or incorporated into the stent or thetubular body after forming.

In some embodiments, the body of the biodegradable material or implantor the body comprising the biodegradable polymer or co-polymer orpolymer blend, is substantially a tube. In other embodiments, it issubstantially oval, or has the shape of substantially the anatomy inwhich the implant is to be deployed into, or substantially the shape inwhich the anatomy is desired to be shaped into. The shape of the bodymay depend on the structure used to form the body shape.

One or more coatings can be applied onto the body of the device. Each ofthe coatings can contain one or more biodegradable polymers, one or morenon-degradable polymers, one or more metals or metal alloys, one or morebiologically active agents, or one or more additives, or a combinationthereof. The coating(s) can serve any of a variety of functions,including controlling degradation of the body of the device, improvingor controlling physical characteristics (e.g., strength, recoil,toughness) of the device, and delivering one or more biologically activeagents to a site of treatment.

In additional embodiments, the biodegradable implantable devicecomprises a first coating disposed over or adjacent to at least aportion of the body of the device, wherein the first coating comprises abiodegradable polymer or a non-degradable polymer or both. Thebiodegradable polymer of the first coating can be any biodegradablepolymer described herein, and the non-degradable polymer of the firstcoating can be any non-degradable polymer described herein. In certainembodiments, the biodegradable polymer of the first coating is apolylactide homopolymer or copolymer, wherein lactide includesL-lactide, D-lactide and D,L-lactide. In some embodiments, thebiodegradable polymer of the first coating is a copolymer of L-lactideand glycolide in a weight or molar ratio of about 70:30 to about99.9:0.1, or about 75:25 to about 95:5, or about 80:20 to about 90:10,or about 82:18 to about 88:12. In an embodiment, the biodegradablepolymer of the first coating is a copolymer of lactide such as L-lactideand glycolide in a weight or molar ratio of about 85:15. In otherembodiments, the biodegradable polymer of the first coating is lactidesuch as poly(L-lactide).

In further embodiments, the first coating comprises one or morebiologically active agents. The biologically active agent(s) of thefirst coating can be any biologically active agent described herein.

In still further embodiments, the first coating comprises one or moreadditives. The additive(s) of the first coating can be any additivedescribed herein. In some embodiments, the additive(s) of the coatingare additive(s) that reduce water absorption, act as a water barrier orreact with water (designed, e.g., to control degradation of the deviceor self-expansion of a self-expandable device). The additive(s) can forma thin layer, or be incorporated in a coating, on any surface of thedevice (e.g., the luminal surface and/or the abluminal surface of astent). As a non-limiting example, the additive(s) can be waxysubstances, such as beeswax. As another example, the additive(s) of thecoating can be salts that react with water, such as calcium salts,magnesium salts or sodium salts. As a further example, the additive(s)can be metals or metal alloys that react with water, such as magnesium,magnesium alloys, iron or iron alloys. The metals or metal alloys can bein any suitable form, such as nanoparticles, microparticles or colloids.

In additional embodiments, the biodegradable implantable devicecomprises a second coating disposed over or adjacent to at least aportion of the first coating, wherein the second coating comprises abiodegradable polymer or a non-degradable polymer or both. Thebiodegradable polymer of the second coating can be any biodegradablepolymer described herein, and the non-degradable polymer of the secondcoating can be any non-degradable polymer described herein.

In further embodiments, the second coating comprises one or morebiologically active agents. The biologically active agent(s) of thesecond coating can be any biologically active agent described herein. Inyet further embodiments, the second coating comprises one or moreadditives. The additive(s) of the second coating can be any additivedescribed herein.

The biodegradable implantable device can comprise a third, fourth oradditional coating, as generally described for the first coating and thesecond coating.

In some embodiments, at least one coating (e.g., the first coating)comprises myolimus or novolimus. In further embodiments, at least onecoating (e.g., the first coating) comprises novolimus and anantioxidant. In an embodiment, the antioxidant is butylatedhydroxytoluene (BHT). In certain embodiments, the weight percent of theantioxidant in the novolimus-containing coating is about 0.1% to about2%, or about 0.1% to about 1%, or about 0.5% to about 1%. In someembodiments, at least one coating (e.g., the first coating) comprisesnovolimus and BHT, wherein the weight percent of the BHT in the coatingis about 0.1% to about 1%.

In further embodiments, at least one coating comprises an antioxidant.In an embodiment, the antioxidant is butylated hydroxytoluene (BHT). Incertain embodiments, the weight percent of the antioxidant in thecoating is about 0.1% to about 10%, or about 0.1% to about 5%, or about0.5% to about 3%, of the percent weight of coating. In anotherembodiment, the at least one coating comprising an antioxidant is a topcoating.

In certain embodiments, at least one coating of the device comprises ananti-proliferative agent, anti-mitotic agent, cytostatic agent,anti-migratory agent or anti-inflammatory agent. In additionalembodiments, at least one coating of the device comprises ananti-proliferative agent, anti-mitotic agent, cytostatic agent,anti-migratory agent or anti-inflammatory agent, and at least onecoating (whether the same or different coating) comprises ananticoagulant, anti-thrombotic agent, thrombolytic agent, anti-thrombinagent, anti-fibrin agent or anti-platelet agent. In further embodiments,the body of the device comprises an anti-proliferative agent,anti-mitotic agent, cytostatic agent, anti-migratory agent oranti-inflammatory agent, and at least one coating of the devicecomprises an anticoagulant, anti-thrombotic agent, thrombolytic agent,anti-thrombin agent, anti-fibrin agent or anti-platelet agent. In yetfurther embodiments, the body of the device comprises an anticoagulant,anti-thrombotic agent, thrombolytic agent, anti-thrombin agent,anti-fibrin agent or anti-platelet agent, and at least one coating ofthe device comprises an anti-proliferative agent, anti-mitotic agent,cytostatic agent, anti-migratory agent or anti-inflammatory agent.

In additional embodiments, the body of a substantially tubular device(e.g., a stent) has an outer (abluminal) layer that contains ananti-proliferative agent, anti-mitotic agent, cytostatic agent,anti-migratory agent or anti-inflammatory agent for preventing orreducing, e.g., any proliferative or inflammatory response at thetreated tissue, and has an inner (luminal) layer that contains ananticoagulant, anti-thrombotic agent, thrombolytic agent, anti-thrombinagent, anti-fibrin agent or anti-platelet agent for preventing orreducing, e.g., any coagulation or thrombosis formation of blood flowingthrough the device. In further embodiments, the outer (abluminal)surface of a substantially tubular device (e.g., a stent) has a coatingthat contains an anti-proliferative agent, anti-mitotic agent,cytostatic agent, anti-migratory agent or anti-inflammatory agent, andthe inner (luminal) surface of the device has a coating that contains ananticoagulant, anti-thrombotic agent, thrombolytic agent, anti-thrombinagent, anti-fibrin agent or anti-platelet agent.

In some embodiments, the thickness (e.g., average thickness) of each ofthe first coating and any additional coating(s) independently is about20 microns or less, or about 15 microns or less, or about 10 microns orless, or about 5 microns or less, or about 4 microns or less, or about 3microns or less, or about 2 microns or less, or about 1 micron or less,or about 0.1 micron or less, or about 0.1 micron or less. In certainembodiments, the thickness (e.g., average thickness) of the firstcoating is about 5 microns or less, or about 3 microns or less.

In further embodiments, the biodegradable copolymer or polymers and anyadditional biodegradable polymer(s), and optionally any non-degradablepolymer(s), comprising the body of the device, a layer of the body or acoating on the body are sufficiently biocompatible and at least somedegrade into by-products (e.g., acidic, basic or neutral substancescorresponding to monomers of the polymers) that are at least somenaturally present in the body of a subject or do not cause significantharmful effect to (e.g., significant injury or toxicity to orsignificant immunological reaction in) the body of the subject. Inadditional embodiments, any corrodible metal(s) or metal alloy(s), andoptionally any non-corrodible metal(s) or metal alloy(s), comprising thebody of the device, a layer of the body or a coating on the body arebiocompatible and degrade into by-products that are naturally present inthe body of a subject or do not cause significant harmful effect to(e.g., significant injury or toxicity to or significant immunologicalreaction in) the body of the subject.

In certain embodiments, the body of the device, a particular layer ofthe body or a coating on the device, or the material (e.g., polymericmaterial) comprising the body of the device, a particular layer of thebody or a coating on the device, is substantially non-porous. In otherembodiments, the body of the device, a particular layer of the body or acoating on the device, or the material (e.g., polymeric material)comprising the body of the device, a particular layer of the body or acoating on the device, is substantially porous.

In another embodiment, the biodegradable polymeric material is treatedat least by heat at a temperature above Tg, preferably between Tg-50 Cabove Tg, before patterning for a time period ranging from 10 seconds to5 hours (at a diameter that is substantially the same as the formeddiameter, or at a diameter that is substantially the same as thepatterned diameter, or at a diameter that is greater than the nominaldeployment diameter of the stent), and then crimping the stent (to asmaller diameter than patterned diameter, or to a smaller diameter thanformed diameter, or to a smaller diameter than nominal deployed diameterof the stent) onto a delivery system at a temperature below Tg for atime period ranging from ten seconds to 60 minutes. The stent at bodytemperature is capable to expand from a crimped configuration to adeployed configuration with sufficient strength to support a body lumen.Optionally, the biodegradable polymeric material is treated at least byheat at a temperature above Tg, preferably between Tg-50° C. above Tg,after patterning for a time period ranging from 10 seconds to 5 hours(at a diameter that is substantially the same as the formed diameter, orat a diameter that is substantially the same as the patterned diameter,or at a diameter that is greater than the nominal deployment diameter ofthe stent), before crimping to a smaller diameter as described above.

An example is a biodegradable stent comprising a polymeric materialformed optionally into a tubular body wherein the polymeric materialcomprises lactide-co-caprolactone (or a blend of lactide andcaprolactone). The tubular body is formed optionally by spraying thepolymeric material onto a mandrel. DCM (or other suitable solventcapable of dissolving completely the polymeric material) is incorporatedinto the solution such that the amount of DCM after treatment is lessthan 1.5% by weight of the polymeric material. The tubular body istreated by heating at a temperature above Tg of the polymeric materialfor a time period ranging from 10 seconds to 5 hours, and/or cooling ata temperature below Tg of the polymeric material, is patterned atsubstantially the same diameter as the formed diameter, and is crimpedonto a delivery system at a temperature below Tg of the polymericmaterial. The stent at body temperature (about 37° C.) is expandablefrom the crimped configuration to an expanded diameter that is 1.2 timesthe nominal deployment diameter (labeled diameter) of the stent withoutfracture and having sufficient strength to support a body lumen.

In another embodiment, the tubular polymeric material is treatedsubstantially without increasing the outer diameter of the tubularmaterial or without substantially changing the diameter of the tube;before patterning or after patterning. In another embodiment, thepolymeric tube is treated to increase the inner diameter of the tubularpolymeric material without substantially increasing the outer diameterof the polymeric tube or without increasing the outer diameter of thetubular body. Examples include treatment of stent or tubular body atsubstantially the same diameter of the formed polymeric tube outerdiameter, by pressure, and/or heat at a temperature above Tg, and/orstretching; before patterning; and then patterning the tubular bodybefore crimping the stent to a smaller diameter onto a delivery systemat a temperature below Tg. The stent at body temperature is capable toexpand from a crimped configuration to an expanded configuration andhave sufficient strength to support a body lumen. For example, a 4.00 mmouter diameter and 3.70 mm inner diameter polymeric tube comprising85:15 poly(L-lactide-co-glycolide) formed by extrusion, spraying,dipping, or the like. This tube is placed inside a metal (or glass) moldwith approximately 4.0 mm diameter cylindrical hole (inner diameter ofthe mold), (or optionally 4.0 mm inner diameter mold, or optionally lessthan 4.0 mm ID mold, or optionally 4.1 mm ID mold, or optionally a moldID with 0.9-1.15 times the formed OD of the polymeric material, oroptionally a mold ID with 0.9-1.1, times the formed OD of the polymericmaterial). The mold optionally could be composed of two halves for easeof tube placement and removal. The mold and/or the polymeric material isheated to above the polymeric material Tg. The ID of the polymericmaterial is pressurized at pressure(s) ranging from 100 psi to 5000 psiin a fraction of a second to 5 minutes, and the polymeric material isoptionally stretched by an amount ranging from 10% to 500% of thepolymeric material length in a time ranging from a fraction of a secondto 5 minutes. The polymeric material is optionally cooled at atemperature below Tg in a time ranging from a fraction of a second to 50minutes. The compressed polymeric tubing with approximately 4.00 mmouter diameter (+/−0.1 mm) and an inner diameter ranging from 3.8 toapproximately 3.6 mm inner diameter is then removed. The wall of thepolymeric tube in this example is compressed approximately 0.0005″. Themodified tube is patterned at substantially the same diameter, andsubsequently coated with a drug or drug-polymer and subsequently crimpedonto a delivery system at a temperature below Tg of the polymericmaterial and then sterilized. The stent at body temperature (about 37°C.) is expandable from the crimped configuration to an expanded diameterhaving sufficient strength to support a body lumen.

In another embodiment, the stent at body temperature is expandable froma crimped configuration to an expanded configuration and have sufficientstrength to support a body lumen wherein the stent expands further inthe body lumen to a diameter larger than the deployed diameter of thestent.

In another embodiment, the stent at body temperature is expandable froma crimped configuration to an expanded configuration and have sufficientstrength to support a body lumen after an inward recoil of less than 15%(or between 1% and 15% inward recoil, or between 2%-10%) from theexpanded configuration wherein the stent further expands in the body toa diameter larger than the deployed diameter (or expanded configuration)of the stent. The further expansion of the stent diameter or area orvolume by at least 5%, by at least 10%, or by at least 15% larger thanthe deployed diameter. The further expansion of the scaffold in the bodylumen occurs after deployment in the body, within 7 days, within 30days, within 6 months, within 1 year, or within 2 years of thedeployment of the stent in the body.

In another embodiment, the stent at body temperature is expandable froma crimped configuration to an expanded configuration and have sufficientstrength to support a body lumen after an inward recoil of less than 15%(or between 1% and 15% inward recoil, or between 2%-10%) from theexpanded configuration wherein the stent further expands in the body toa diameter larger than the deployed diameter (or expanded configuration)of the stent and wherein the lumen further expands to a diameter (orarea or volume) larger than lumen diameter (or area or volume) atdeployment. The further expansion of the lumen diameter or area orvolume is by at least 5%, by at least 10%, or by at least 15% largerthan the lumen diameter or area or volume at deployment. The furtherexpansion of the body lumen occurs after deployment of the stent in thebody, within 7 days, within 30 days, within 6 months, within 1 year, orwithin 2 years after the deployment of the stent in the body. The stentand body lumen diameter or area or volume can be measured by QCA, IVUS,OCT, or MSCT.

In further embodiments, the body of the device, or the stent, or thematerial comprising the body of the device, or the material comprisingone or more layers of the body of the device, comprises one or morebiologically active agents. In some embodiments, the biologically activeagent(s) are selected from the group consisting of anti-proliferativeagents, anti-mitotic agents, cytostatic agents, anti-migratory agents,immunomodulators, immunosuppressants, anti-inflammatory agents,anticoagulants, anti-thrombotic agents, thrombolytic agents,anti-thrombin agents, anti-fibrin agents, anti-platelet agents,anti-ischemia agents, anti-hypertensive agents, anti-hyperlipidemiaagents, anti-diabetic agents, anti-cancer agents, anti-tumor agents,anti-angiogenic agents, angiogenic agents, anti-bacterial agents,anti-fungal agents, anti-chemokine agents, and healing-promoting agents.In certain embodiments, the body of the device comprises ananti-proliferative agent, anti-mitotic agent, cytostatic agent oranti-migratory agent. In further embodiments, the body of the devicecomprises an anticoagulant, anti-thrombotic agent, thrombolytic agent,anti-thrombin agent, anti-fibrin agent or anti-platelet agent inaddition to an anti-proliferative agent, anti-mitotic agent, cytostaticagent or anti-migratory agent. It is appreciated that specific examplesof biologically active agents disclosed herein may exert more than onebiological effect.

Examples of anti-proliferative agents, anti-mitotic agents, cytostaticagents and anti-migratory agents include without limitation inhibitorsof mammalian target of rapamycin (mTOR), rapamycin (also calledsirolimus), deuterated rapamycin, TAFA93, 40-O-alkyl-rapamycinderivatives, 40-O-hydroxyalkyl-rapamycin derivatives, everolimus{40-O-(2-hydroxyethyl)-rapamycin}, 40-O-(3-hydroxyl)propyl-rapamycin,40-O-[2-(2-hydroxyl)ethoxy]ethyl-rapamycin, 40-O-alkoxyalkyl-rapamycinderivatives, biolimus {40-O-(2-ethoxyethyl)-rapamycin},40-O-acyl-rapamycin derivatives, temsirolimus{40-(3-hydroxy-2-hydroxymethyl-2-methylpropanoate)-rapamycin, orCCI-779}, 40-O-phospho-containing rapamycin derivatives, ridaforolimus(40-dimethylphosphinate-rapamycin, or AP23573), 40(R or S)-heterocyclyl-or heteroaryl-containing rapamycin derivatives, zotarolimus{40-epi-(N1-tetrazolyl)-rapamycin, or ABT-578},40-epi-(N2-tetrazolyl)-rapamycin, 32(R or S)-hydroxy-rapamycin, myolimus(32-deoxo-rapamycin), novolimus (16-O-desmethyl-rapamycin), AP20840,AP23464, AP23675, AP23841, taxanes, paclitaxel, docetaxel,cytochalasins, cytochalasins A through J, latrunculins, and salts,isomers, analogs, derivatives, metabolites, prodrugs and fragmentsthereof. The IUPAC numbering system for rapamycin is used herein. Incertain embodiments, the body of the device comprises myolimus ornovolimus.

Table 1 provides non-limiting examples of derivatives of each ofrapamycin, everolimus, biolimus, temsirolimus, ridaforolimus,zotarolimus, myolimus and novolimus.

TABLE 1 Derivatives of rapamycin-type compounds Derivatives of Each ofRapamycin, Everolimus, Biolimus, Temsirolimus, Ridaforolimus,Zotarolimus, Myolimus and Novolimus N7-oxide 2-hydroxy 3-hydroxy4-hydroxy 5-hydroxy 6-hydroxy 11-hydroxy 12-hydroxy 13-hydroxy14-hydroxy 23-hydroxy 24-hydroxy 25-hydroxy 31-hydroxy 35-hydroxy43-hydroxy (11-hydroxymethyl) 44-hydroxy (17-hydroxymethyl) 45-hydroxy(23-hydroxymethyl) 46-hydroxy (25-hydroxymethyl) 47-hydroxy(29-hydroxymethyl) 48-hydroxy (31-hydroxymethyl) 49-hydroxy(35-hydroxymethyl) 17,18-dihydroxy 19,20-dihydroxy 21,22-dihydroxy29,30-dihydroxy 10-phosphate 28-phosphate 40-phosphate 16-O-desmethyl27-O-desmethyl 39-O-desmethyl 16,27-bis(O-desmethyl)16,39-bis(O-desmethyl) 27,39-bis(O-desmethyl) 16,27,39-tris(O-desmethyl)16-desmethoxy 27-desmethoxy 39-O-desmethyl-14-hydroxy 17,18-epoxide19,20-epoxide 21,22-epoxide 29,30-epoxide 17,18-29,30-bis-epoxide17,18-19,20-21,22-tris-epoxide 19,20-21,22-29,30-tris-epoxide16-O-desmethyl-17,18-19,20-bis-epoxide16-O-desmethyl-17,18-29,30-bis-epoxide16-O-desmethyl-17,18-19,20-21,22-tris-epoxide16-O-desmethyl-19,20-21,22-29,30-tris-epoxide27-O-desmethyl-17,18-19,20-21,22-tris-epoxide39-O-desmethyl-17,18-19,20-21,22-tris-epoxide16,27-bis(O-desmethyl)-17,18-19,20-21,22-tris-epoxide16-O-desmethyl-24-hydroxy-17,18-19,20-bis-epoxide16-O-desmethyl-24-hydroxy-17,18-29,30-bis-epoxide 12-hydroxy and openedhemiketal ring

Examples of immunomodulators and immunosuppressants include, but are notlimited to, tacrolimus (also called FK-506), ascomycin, pimecrolimus,TKB662, cyclosporins, cyclosporine (also called cyclosporin A),cyclosporin G, vocyclosporin, myriocin, and salts, isomers, analogs,derivatives, metabolites, prodrugs and fragments thereof. In certainembodiments, the body of the device (or a coating on the device)comprises tacrolimus.

Non-limiting examples of anti-inflammatory agents include non-steroidalanti-inflammatory drugs (NSAIDs); salicylates, aspirin, diflunisal,salsalate; propionic acid derivatives, ibuprofen, naproxen, fenoprofen,flurbiprofen, ketoprofen, oxaprozin; acetic acid derivatives,diclofenac, etodolac, indomethacin, ketorolac, nabumetone, sulindac,tetradecylthioacetic acid, tolmetin; enolic acid derivatives, droxicam,isoxicam, lornoxicam, meloxicam, piroxicam, tenoxicam; fenamic acidderivatives, flufenamic acid, meclofenamic acid, mefenamic acid,tolfenamic acid; cyclooxygenase-2 (COX-2) inhibitors, celecoxib,etoricoxib, lumiracoxib, parecoxib, parecoxib sodium, rofecoxib,valdecoxib, sulfonanilides, nimesulide, flosulide, acetaminophen,o-(acetoxyphenyl)hept-2-ynyl-2-sulfide (APHS), DuP-697, JTE-522,L-745337, L-748780, L-761066,N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398),RS-57067, S-2474, SC-57666, SC-58125; lipooxygenase (LOX)/cyclooxygenase(COX) inhibitors, licofelone; glucocorticoids, beclometasone,betamethasone, cortisol (hydrocortisone), cortisone, cortisone acetate,dexamethasone, dexamethasone acetate, dexamethasone phosphate,fluprednisolone, fluticasone, fluticasone propionate, meprednisone,methylprednisone, methylprednisolone, paramethasone, prednisolone,prednisone, triamcinolone; pseudopterosins; and salts, isomers, analogs,derivatives, metabolites, prodrugs and fragments thereof. In certainembodiments, the body of the device (or a coating on the device)comprises dexamethasone.

Examples of anticoagulants, anti-thrombotic agents, thrombolytic agents,anti-thrombin agents, anti-fibrin agents, and anti-platelet agentsinclude without limitation catechins, including (+)-catechin and(−)-catechin, epicatechins, including (+)-epicatechin and(−)-epicatechin, epigallocatechin-3-O-gallate, vitamin K antagonists,4-hydroxycoumarins, warfarin, acenocoumarol, brodifacoum, coumatetralyl,dicoumarol, phenprocoumon, tioclomarol, 1,3-indandiones, clorindione,diphenadione, fluindione, phenindione, factor Xa inhibitors, apixaban,betrixaban, rivaroxaban, DU-176b, LY-517717, YM-150, heparin, lowmolecular weight heparin, nadroparin (Fraxiparine®), heparin analogs,fondaparinux (Arixtra®), idraparinux, thrombin/factor IIa inhibitors,argatroban, dabigatran, ximelagatran, melagatran, AZD-0837, hirudin,hirudin analogs, bivalirudin, desirudin, lepirudin, COX inhibitors,aspirin, adenosine diphosphate (ADP) receptor inhibitors, clopidogrel(Plavix®), prasugrel, ticlopidine, phosphodiesterase (PDE) inhibitors,cilostazol, glycoprotein IIb/IIIA inhibitors, abciximab, eptifibatide,tirofiban, adenosine reuptake inhibitors, dipyridamole, cytochalasins,cytochalasin B, cytochalasin D, epoprostenol, anistreplase,streptokinase, urokinase, tissue plasminogen activators (t-PAs),alteplase, reteplase, tenecteplase, and salts, isomers, analogs,derivatives, metabolites, prodrugs and fragments thereof. In certainembodiments, the body of the device (or a coating on the device)comprises argatroban, dabigatran, rivaroxaban, low molecular weightheparin, warfarin, aspirin or clopidogrel, or a combination thereof.

Examples of anti-ischemia agents include, but are not limited to,isosorbide dinitrate, ranolazine, and salts, isomers, analogs,derivatives, metabolites, prodrugs and fragments thereof.

Non-limiting examples of anti-hypertensive agents includeangiotensin-converting enzyme (ACE) inhibitors, captopril, cilazapril,lisinopril, calcium channel blockers, amlodipine, nifedipine, adalat,atenolol, candesartan, diovan, diltiazem, and salts, isomers, analogs,derivatives, metabolites, prodrugs and fragments thereof.

Examples of anti-hyperlipidemia agents include without limitationHMG-CoA reductase inhibitors; statins, atorvastatin, cerivastatin,fluvastatin, lovastatin, mevastatin, pitavastatin, pravastatin,rosuvastatin, simvastatin; fibrates, bezafibrate, ciprofibrate,clofibrate, aluminium clofibrate, etofibrate, fenofibrate, gemfibrozil;bile acid sequestrants, cholestyramine, colesevelam, colestipol;ezetimibe, niacin; and salts, isomers, analogs, derivatives,metabolites, prodrugs and fragments thereof.

Non-limiting examples of anti-diabetic agents include biguanides,buformin, metformin, phenformin; meglitinides, nateglinide, repaglinide;sulfonylureas, acetohexamide, chlorpropamide, glibenclamide (also calledglyburide), gliclazide, glimepiride, glipizide, gliquidone,glyclopyramide, tolazamide, tolbutamide; agonists of peroxisomeproliferator-activated receptors γ (PPARγ), thiazolidinediones,ciglitazone, MCC-555, pioglitazone, rivoglitazone, rosiglitazone,troglitazone; dipeptidyl peptidase-4 inhibitors, alogliptin, berberine,dutogliptin, gemigliptin, linagliptin, saxagliptin, sitagliptin,vildagliptin; and salts, isomers, analogs, derivatives, metabolites,prodrugs and fragments thereof.

Examples of anti-cancer agents and anti-tumor agents include withoutlimitation ABJ879, acivicin, aclarubicin, acodazole, acronycine,actinomycins, actinomycin D (dactinomycin), adozelesin, alanosine,aldesleukin, allopurinol, allopurinol sodium, altretamine,aminoglutethimide, amonafide, ampligen, amsacrine, androgens, anguidine,antiopeptin, aphidicolin, aphidicolin glycinate, asaley, asparaginase,5-azacitidine, azathioprine, Bacillus Calmette-Guerin (BCG), methanolextraction residue of Bacillus Calmette-Guerin, Baker's Antifol(soluble), beta-2′-deoxythioguanosine, bisantrene, bisantrene HCL,bleomycin, bleomycin sulfate, BMS-247550, busulfan, buthioninesulfoximine, BWA 773U82, BW 502U83, BW 502U83 HCl, BW 7U85, BW 7U85mesylate, ceracemide, carbetimer, carboplatin, carmustine, chlorambucil,2-chlorodeoxyadenosine, chloroquinoxaline sulfonamide, chlorozotocin,chromomycins, chromomycin A3 (toyomycin), cisplatin, cladribine,corticosteroids, Corynebacterium parvum, CPT-11, crisnatol,cyclocytidine, cyclophosphamide, cytarabine, cytembena, dabis maleate{(1,4-bis(2′-chloroethyl)-1,4-diaza-bicyclo[2.2.1]heptane dihydrogendimaleate}, dacarbazine, daunorubicin, daunorubicin HCl, deazauridine,denibulin (MN-029), dexrazoxane, dianhydrogalactitol, diaziquone,dibromodulcitol, didemnins, didemnin B, diethyldithiocarbamate,diglycoaldehyde, dihydro-5-azacytidine, doxorubicin, echinomycin,ecteinascidins, edatrexate, edelfosine, eflomithine, Elliott's solution,elsamitrucin, epirubicin, epothilones, epothilone B, epothilone C,epothilone D, esorubicin, estramustine, estramustine phosphate,estrogens, ET-743, etanidazole, ethiofos, etoposide, fadrazole,fazarabine, fenretinide, filgrastim, finasteride, flavones, flavoneacetic acid, floxuridine, fludarabine phosphate, 5-fluorouracil,Fluosol®, flutamide, gallium nitrate, gemcitabine, goserelin, goserelinacetate, hepsulfam, hexamethylene bisacetamide, homoharringtonine,hydrazine, hydrazine sulfate, 4-hydroxyandrostenedione, hydroxyurea,idarubicin, idarubicin HCl, ifosfamide, interferons, interferon-α,interferon-β, interferon-γ, interleukins, interleukin-1 alpha and beta,interleukin-3, interleukin-4, interleukin-6, 4-ipomeanol, iproplatin,irinotecan, isotretinoin, leucovorin, leucovorin calcium, leuprolide,leuprolide acetate, levamisole, liposomal daunorubicin,liposome-encapsulated doxorubicin, lomustine, lonidamine, maytansine,mechlorethamine, mechlorethamine hydrochloride, melphalan, menogaril,merbarone, 6-mercaptopurine, mesna, methotrexate, N-methylformamide,mifepristone, mitoguazone, mitomycins, mitomycin C, mitotane,mitoxantrone, mitoxantrone hydrochloride, monocyte/macrophagecolony-stimulating factor, nabilone, nafoxidine, neocarzinostatin,octreotide, octreotide acetate, ormaplatin, oxaliplatin, patupilone,N-phosphonacetyl-L-aspartate (PALA), pentostatin, piperazinedione,pipobroman, pirarubicin, pirfenidone, piritrexim, piroxantrone,piroxantrone HCl, PIXY-321, plicamycin, porfimer sodium, prednimustine,procarbazine, progestins, pyrazofurin, QP-2, razoxane, sargramostim,semustine, sirolimus, spirogermanium, spiromustine, streptonigrin,streptozocin, sulofenur, suramin, suramin sodium, tamoxifen, taxanes,docetaxel (Taxotere®), paclitaxel (Taxol®), tegafur, teniposide,terephthalamidine, teroxirone, tetrahydroisoquinoline alkaloids,thioguanine, thiotepa, thymidine, tiazofurin, topotecan, toremifene,tretinoin, trifluoperazine, trifluoperazine HCl, trifluridine,trimetrexate, tumor necrosis factor, uracil mustard, vinca alkaloids,vinblastine, vinblastine sulfate, vincristine, vincristine sulfate,vindesine, vinorelbine, vinzolidine, Yoshi 864, zorubicin, and salts,isomers, analogs, derivatives, metabolites, prodrugs and fragmentsthereof. In certain embodiments, the body of the device (or a coating onthe device) comprises docetaxel or paclitaxel.

Non-limiting examples of anti-angiogenic agents include angioarrestin,angiostatin, antithrombin III fragment, calreticulin, canstatin,endostatin, thrombospondin 1 (TSP-1), TSP-2, tumistatin, vasculostatin,vasostatin, vascular endothelial growth factor (VEGF) inhibitors,bevacizumab, prolactin, matrix metalloproteinase inhibitors, batimastat,marimastat, prinomastat, angiostatic steroids, 2-methoxyestradiol,carboxyamidotriazole, cytochalasins, cytochalasin E, linomide,retinoids, suramin, tecogalan, thalidomide, TNP-470, and salts, isomers,analogs, derivatives, metabolites, prodrugs and fragments thereof.

Examples of angiogenic agents include, but are not limited to,angiogenin, angiopoietin-1, becaplermin, follistatin, leptin, midkine,and salts, isomers, analogs, derivatives, metabolites, prodrugs andfragments thereof.

Anti-bacterial agents include chelators, antibiotics, bacteriostaticagents, bacteriocidal agents, and anti-septic agents. Non-limitingexamples of anti-bacterial agents include aminoglycosides, amikacin,gentamicin, kanamycin, neomycin, netilmicin, tobramycin, paromomycin;ansamycins, geldanamycin, herbimycin; carbacephems, loracarbef;carbapenems, ertapenem, doripenem, imipenem (cilastatin), meropenem;first-generation cephalosporins, cefadroxil, cefazolin, cefalotin(cefalothin), cefalexin; second-generation cephalosporins, cefaclor,cefamandole, cefoxitin, cefprozil, cefuroxime; third-generationcephalosporins, cefixime, cefdinir, cefditoren, cefoperazone,cefotaxime, cefpodoxime, ceftazidime, ceftibuten, ceftizoxime,ceftriaxone; fourth-generation cephalosporins, cefepime;fifth-generation cephalosporins, ceftobiprole; glycopeptides,teicoplanin, vancomycin, telavancin; lincosamides, clindamycin,lincomycin; lipopeptides, daptomycin; macrolides, azithromycin,clarithromycin, dirithromycin, erythromycin, roxithromycin,troleandomycin, telithromycin, spectinomycin; monobactams, aztreonam;nitrofurans, furazolidone, nitrofurantoin; penicillins, amoxicillin,ampicillin, azlocillin, carbenicillin, cloxacillin, dicloxacillin,flucloxacillin, mezlocillin, methicillin, nafcillin, oxacillin,penicillin G, penicillin V, piperacillin, temocillin, ticarcillin;penicillin-containing combinations, amoxicillin/clavulanate,ampicillin/sulbactam, piperacillin/tazobactam, ticarcillin/clavulanate;polypeptides, bacitracin, colistin, polymyxin B; quinolones,ciprofloxacin, enoxacin, gatifloxacin, levofloxacin, lomefloxacin,moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, trovafloxacin,grepafloxacin, sparfloxacin, temafloxacin; sulfonamides, mafenide,sulfonamidochrysoidine, sulfacetamide, sulfadiazine, silversulfadiazine, sulfamethizole, sulfamethoxazole, sulfanilimide,sulfasalazine, sulfisoxazole, trimethoprim,trimethoprim-sulfamethoxazole (co-trimoxazole); tetracyclines,demeclocycline, doxycycline, minocycline, oxytetracycline, tetracycline;anti-mycobacteria agents, clofazimine, dapsone, capreomycin,cycloserine, ethambutol, ethionamide, isoniazid, pyrazinamide,rifampicin (rifampin), rifabutin, rifapentine, streptomycin;arsphenamine, chloramphenicol, fosfomycin, fusidic acid, linezolid,metronidazole, mupirocin, platensimycin, quinupristin/dalfopristin,rifaximin, thiamphenicol, tinidazole; and salts, isomers, analogs,derivatives, metabolites, prodrugs and fragments thereof.

Examples of anti-fungal agents include without limitation polyeneantifungals, amphotericins, amphotericin B, candicin, filipin, hamycin,natamycin, nystatin, rimocidin; inhibitors of lanosterol14α-demethylase; imidazole antifungals, bifonazole, butoconazole,clotrimazole, econazole, fenticonazole, isoconazole, ketoconazole,miconazole, omoconazole, oxiconazole, sertaconazole, sulconazole,tioconazole; triazole antifungals, fluconazole, isavuconazole,itraconazole, posaconazole, ravuconazole, terconazole, voriconazole;thiazole antifungals, abafungin; squalene epoxidase inhibitors;allylamine antifungals, butenafine, naftifine, terbinafine; inhibitorsof 1,3-β glucan synthase; echinocandins, anidulafungin, caspofungin,micafungin; allicin, ciclopirox, ECO-4601, farnesylateddibenzodiazepinone, 5-fluorocytosine, griseofulvin, haloprogin,polygodial, tolnaftate, undecylenic acid; and salts, isomers, analogs,derivatives, metabolites, prodrugs and fragments thereof.

Examples of anti-chemokine agents include, but are not limited to,3-acylaminolactams, acylaminocaprolactams, 3-acylaminoglutarimides,FX125L, and salts, isomers, analogs, derivatives, metabolites, prodrugsand fragments thereof.

For a vessel-contacting device (e.g., a stent), in some embodiments ahealing-promoting agent can promote re-endothelialization of a damagedvessel (e.g., blood vessel) to promote healing of the damaged tissue.The portion(s) of the device containing a healing-promoting agent canattract, bind and become encapsulated by endothelial cells (e.g.,endothelial progenitor cells, which help repair damage blood vessels),which can reduce or prevent formation of emboli or thrombi. In certainembodiments, healing-promoting agents are endothelial cell-bindingagents (including endothelial progenitor cell-binding agents), includingwithout limitation an active fragment of osteopontin(Asp-Val-Asp-Val-Pro-Asp-Gly-Asp-Ser-Leu-Ala-Try-Gly), RGD-containingpeptide sequences, RGD mimetics, collagen type 1, single chain Fvfragment (scFv A5), junction membrane protein vascularendothelial-cadherin, epithelial cell antibodies, CD-34, CD-133,vascular endothelial growth factor (VEGF) type 2 receptor, and fragmentsthereof.

In certain embodiments, the body of the device (and/or one or morecoatings on the device) comprises one or more biologically active agentsselected from the group consisting of mTOR inhibitors, rapamycin,TAFA93, rapamycin derivatives, 40-O-alkyl-rapamycin derivatives,40-O-hydroxyalkyl-rapamycin derivatives, everolimus,40-O-(3-hydroxyl)propyl-rapamycin,40-O-12-(2-hydroxyl)ethoxylethyl-rapamycin, 40-O-alkoxyalkyl-rapamycinderivatives, biolimus, 40-O-acyl-rapamycin derivatives, temsirolimus,40-O-phospho-containing rapamycin derivatives, ridaforolimus, 40(R orS)-heterocyclyl- or heteroaryl-containing rapamycin derivatives,zotarolimus, 40-epi-(N2-tetrazolyl)-rapamycin, 32(R orS)-hydroxy-rapamycin, myolimus, novolimus, AP20840, AP23464, AP23675,AP23841, taxanes, paclitaxel, docetaxel, cytochalasins, latrunculins,tacrolimus, ascomycin, pimecrolimus, TKB662, cyclosporins, cyclosporine,cyclosporin G, vocyclosporin, myriocin, non-steroidal anti-inflammatorydrugs, salicylates, propionic acid derivatives, acetic acid derivatives,enolic acid derivatives, fenamic acid derivatives, COX-2 inhibitors,LOX/COX inhibitors, glucocorticoids, betamethasone, dexamethasone,methylprednisolone, pseudopterosins, catechins, epicatechins,epigallocatechin-3-O-gallate, vitamin K antagonists, 4-hydroxycoumarins,warfarin, acenocoumarol, brodifacoum, coumatetralyl, dicoumarol,phenprocoumon, tioclomarol, 1,3-indandiones, clorindione, diphenadione,fluindione, phenindione, factor Xa inhibitors, apixaban, betrixaban,rivaroxaban, DU-176b, LY-517717, YM-150, heparin, low molecular weightheparin, nadroparin (Fraxiparine®), heparin analogs, fondaparinux(Arixtra®), idraparinux, thrombin/factor IIa inhibitors, argatroban,dabigatran, ximelagatran, melagatran, AZD-0837, hirudin, hirudinanalogs, bivalirudin, desirudin, lepirudin, COX inhibitors, aspirin,adenosine diphosphate (ADP) receptor inhibitors, clopidogrel (Plavix®),prasugrel, ticlopidine, phosphodiesterase (PDE) inhibitors, cilostazol,glycoprotein IIb/IIIA inhibitors, abciximab, eptifibatide, tirofiban,adenosine reuptake inhibitors, dipyridamole, cytochalasin B,cytochalasin D, epoprostenol, anistreplase, streptokinase, urokinase,tissue plasminogen activators (t-PAs), alteplase, reteplase,tenecteplase, isosorbide dinitrate, ranolazine, angiotensin-convertingenzyme inhibitors, captopril, cilazapril, lisinopril, calcium channelblockers, amlodipine, nifedipine, adalat, atenolol, candesartan, diovan,diltiazem, HMG-CoA reductase inhibitors, statins, fibrates, bile acidsequestrants, ezetimibe, niacin sulfonylurea anti-diabetics, biguanides,meglitinides, PPARy agonists, thiazolidinediones, dipeptidyl peptidase-4inhibitors, actinomycins, actinomycin D, azathioprine, bleomycin,busulfan, chlorambucil, cyclophosphamide, daunorubicin, didemnins,didemnin B, doxorubicin, epothilones, epothilone B, etoposide,5-fluorouracil, gemcitabine, irinotecan, methotrexate, mitomycin,mitoxantrone, pirfenidone, plicamycin, procarbazine, tamoxifen,topotecan, vinca alkaloids, vinblastine, vincristine, angioarrestin,angiostatin, antithrombin III fragment, calreticulin, canstatin,endostatin, thrombospondin 1 (TSP-1), TSP-2, tumistatin, vasculostatin,vasostatin, VEGF inhibitors, bevacizumab, prolactin, matrixmetalloproteinase inhibitors, batimastat, marimastat, prinomastat,angiostatic steroids, 2-methoxyestradiol, carboxyamidotriazole,cytochalasin E, linomide, retinoids, suramin, tecogalan, thalidomide,TNP-470, angiogenin, angiopoietin-1, becaplermin, follistatin, leptin,midkine, β-lactam antibiotics, cephalosporins, penicillins, monobactamantibiotics, aminoglycoside antibiotics, glycopeptide antibiotics,lipopeptide antibiotics, polypeptide antibiotics, ansamycins,carbacephems, carbapenems, lincosamides, macrolide antibiotics,nitrofuran antibiotics, quinolone antibiotics, sulfonamide antibiotics,tetracyclines, anti-mycobacteria agents, chloramphenicol, linezolid,thiamphenicol, allylamine antifungals, echinocandins, polyeneantifungals, imidazole antifungals, triazole antifungals, thiazoleantifungals, ECO-4601, farnesylated dibenzodiazepinone, griseofulvin,3-acylaminolactams, acylaminocaprolactams, 3-acylaminoglutarimides,FX125L, endothelial cell-binding agents, and salts, isomers, analogs,derivatives, prodrugs, metabolites and fragments thereof.

Depending in part on the type of device it is, the biodegradableimplantable device described herein can be used to treat or prevent awide variety of diseases, disorders and conditions, or promote a widevariety of therapeutic effects. In some embodiments, the biodegradabledevice is implanted in a subject for treatment or prevention of adisorder or condition, or promotion of a therapeutic effect, selectedfrom the group consisting of wound healing, hyper-proliferative disease,cancer, tumor, vascular disease, cardiovascular disease, coronary arterydisease, peripheral arterial disease, atherosclerosis, thrombosis,vulnerable plaque, stenosis, restenosis, ischemia, myocardial ischemia,peripheral ischemia, limb ischemia, hyper-calcemia, vascularobstruction, vascular dissection, vascular perforation, aneurysm,vascular aneurysm, aortic aneurysm, abdominal aortic aneurysm, cerebralaneurysm, chronic total occlusion, patent foramen ovale, hemorrhage,claudication, diabetic disease, pancreas obstruction, kidneyobstruction, bile duct obstruction, intestine obstruction, duodenumobstruction, colon obstruction, ureter obstruction, urethra obstruction,sphincter obstruction, airway obstruction, anastomosis, anastomoticproliferation of artery, vein or artificial graft, bone injury, bonecrack, bone fracture, osteoporosis, skeletal defect, bone defect, weakbone, bone thinning, improper bone union or healing, fusing bone, fusionof adjacent vertebrae, osteochondral defect, chondral defect, cranialdefect, scalp defect, calvarial defect, craniofacial defect,craniomaxillofacial defect, segmental bone loss, thoracic cage defect,cartilage defect, cartilage repair, cartilage regeneration,bone-cartilage bridging, bone-tendon bridging, spinal disorder,scoliosis, nerve damage, nerve injury, nerve defect, nerve repair, nervereconstruction, nerve regeneration, herniation, abdominal herniation,disc herniation, acute or chronic low back pain, discogenic pain,trauma, abdominal wall defect, septal repair, burn injury, facialreconstruction, facial regeneration, aging, and contraception. Thebiodegradable device can also be used outside the body, e.g., in tissueengineering to generate tissue.

When the biodegradable device is a stent, the stent can also be used totreat or prevent a wide variety of diseases, disorders and conditions.In some embodiments, the biodegradable stent is implanted in a subjectfor treatment or prevention of obstruction, occlusion, constriction,stricture, narrowing, stenosis, restenosis, intimal hyperplasia,collapse, dissection, thinning, perforation, kinking, aneurysm, failedaccess graft, cancer or tumor of a vessel, passage, conduit, tubulartissue or tubular organ, such as an artery, vein, peripheral artery,peripheral vein, subclavian artery, superior caval vein, inferior cavalvein, popliteal artery, popliteal vein, arterial duct, coronary artery,carotid artery, brain artery, aorta, ductus arteriosus, rightventricular outflow tract conduit, transitional atrioventricular canal,interatrial septum, iliac artery, common iliac artery, external iliacartery, internal iliac artery, iliac vein, internal pudendal artery,mammary artery, femoral artery, superficial femoral artery, femoralvein, pancreatic artery, pancreatic duct, renal artery, hepatic artery,splenic artery, biliary artery, bile duct, stomach, small intestine,duodenum, jejunum, ileum, large intestine, cecum, colon, rectosigmoidcolon, sphincter, rectum, colorectum, ureter, urethra, prostatic duct,pulmonary artery, aortopulmonary collateral artery, aortopulmonarycollateral vessel, airway, nasal passage, nostril, throat, pharynx,larynx, esophagus, epiglottis, glottis, trachea, carina, bronchus,bilateral main bronchus, intermediate branch bronchus, transbronchialpassage, or tracheobronchus.

Obstruction, occlusion, constriction, stricture, narrowing, stenosis,restenosis, intimal hyperplasia, collapse, dissection, thinning,perforation, kinking, aneurysm, failed access graft, cancer or tumor ofa vessel, passage, conduit, tubular tissue or tubular organ can beassociated with any of a variety of diseases, disorders and conditions,such as atherosclerosis, hardening of the artery (e.g., with fatty acid,cholesterol or calcium), thrombosis, vulnerable plaque, hypertension,diabetes mellitus, brain aneurysm, amyloidosis, congenital heartdisease, chronic stable angina, unstable angina, myocardial infarction,acute myocardial infarction, aortic aneurysm, abdominal aortic aneurysm,thoracic aortic aneurysm, aortic tearing, aortic recoarctation, patentductus arteriosus, atrial septal defect, ventricular septal defect,right ventricular hypoplasia, pulmonary atresia, vascular anomaly,vascular malformation, dextro-transposition of the great arteries,pancreatitis, pancreatic divisum, chronic renal disease, acute renalfailure, primary sclerosing cholangitis, inflammatory bowel disease,Crohn's disease, mucous colitis, ulcerative colitis, diverticulitis,colonic fistula, detrusor external sphincter dyssynergia, enlargedprostate, benign prostatic hyperplasia, lower urinary tract symptom,recurrent bulbar urethral stricture, erectile dysfunction, deviatedseptum, kyphoscoliosis, sarcoidosis, diphtheria, lung disease,tuberculosis, Wegener's granulomatosis, emphysema, cystic fibrosis,respiratory distress, asthma, respiratory infection, respiratorypapillomatosis, chronic obstructive pulmonary disease, bronchitis,intrinsic airway obstruction, apnea, dyspnea, blunt or sharp laryngealtrauma, laryngotracheal disorder, laryngotracheal reconstruction,tracheal trauma or rupture, tracheobronchial disease, tracheal tear,tracheoesophageal fistula, tracheomalacia, bronchomalacia,tracheobronchomalacia, vocal fold paralysis, bilateral vocal foldmobility impairment, epiglottitis, idiopathic progressive subglotticstenosis, dysphagia, intrinsic compression, extrinsic compression, orthyroid goiter.

In some embodiments, the biodegradable stent is implanted in a subjectfor treatment or prevention of wound healing, hyper-proliferativedisease, vascular disease, cardiovascular disease, coronary arterydisease, peripheral arterial disease, atherosclerosis, thrombosis,vulnerable plaque, stenosis, restenosis, ischemia, myocardial ischemia,peripheral ischemia, limb ischemia, hyper-calcemia, vascularobstruction, vascular dissection, vascular perforation, vascularaneurysm, aortic aneurysm, abdominal aortic aneurysm, cerebral aneurysm,chronic total occlusion, patent foramen ovale, hemorrhage, claudication,pancreas obstruction, kidney obstruction, bile duct obstruction,intestine obstruction, duodenum obstruction, colon obstruction, ureterobstruction, urethra obstruction, sphincter obstruction, airwayobstruction, anastomosis, or anastomotic proliferation of artery, veinor artificial graft. In certain embodiments, the stent is implanted in asubject for treatment or prevention of a hyper-proliferative disease, avascular disease or restenosis.

The biodegradable implantable device described herein can be any of awide variety of devices and can have any shape, configuration or formsuitable for its intended function or site of implantation. For example,the body of the device can have a shape suitable for the anatomy inwhich the device is intended to be implanted. In certain embodiments,the body of the device is substantially tubular. The device can serveany of a variety of functions, such as supporting a bodily tissue orstructure (e.g., a vessel), holding together bodily tissues orstructures (e.g., bones), plugging or closing an opening (e.g., awound), containing a synthetic or natural material useful for exerting atherapeutic effect (e.g., endothelial progenitor cells), delivering adrug or a biologic (e.g., an anti-proliferative agent) to a site oftreatment, or a combination thereof.

In some embodiments, the biodegradable device is selected from the groupconsisting of drug-delivery devices, parenteral drug-delivery devices,biologic-delivery devices, vascular implants, luminal implants, stents,stent-grafts, graft implants, grafts, catheters, abdominal aorticaneurysm coils, cerebral aneurysm coils, wound closure implants,sutures, urinary tract implants, organ implants, orthopedic implants,bone implants, dental implants, defect scaffolds, fixation plates,fusion spacers, internal fixators for long bone shafts, spinalcorrectors, spine stabilizers, spine restrictors, spinal fixators,spinal fusion implants, spinal disks, vertebral spacers, intervertebralspacers, bone fusers, bone replacement implants, bone-loss replacements,bone fillers, bone plugs, bone plates, bone fixation devices, bonescrews, bridges, spacers, defect fillers, craniomaxillofacial surgerypatches, craniofacial scaffolds, nerve regeneration implants, nerveguide tubes, nerve conduits, nerve protectors, tendon protectors,staples, staple line reinforcements, osteotomy staples, anastomosisstaples, anastomosis fasteners, septal repair implants, skin patches,skin substitutes, intrauterine implants, and contraceptive devices.

In certain embodiments, the biodegradable device is a stent.Non-limiting examples of stents include vascular stents, coronarystents, coronary heart disease (CHD) stents, carotid stents, brainaneurysm stents, peripheral stents, peripheral vascular stents, venousstents, femoral stents, superficial femoral artery (SFA) stents,pancreatic stents, renal stents, biliary stents, intestinal stents,duodenal stents, colonic stents, ureteral stents, urethral stents,prostatic stents, sphincter stents, airway stents, tracheobronchialstents, tracheal stents, laryngeal stents, esophageal stents, singlestents, segmented stents, joined stents, overlap stents, tapered stents,and bifurcated stents. In certain embodiments, the biodegradable deviceis a vascular or coronary stent.

Biodegradable implantable devices described herein can be stents.Non-limiting examples of stents include vascular stents, coronarystents, coronary heart disease (CHD) stents, carotid stents, brainaneurysm stents, peripheral stents, peripheral vascular stents, venousstents, femoral stents, superficial femoral artery (SFA) stents,pancreatic stents, renal stents, biliary stents, duodenal stents,colonic stents, ureteral stents, urethral stents, prostatic stents,sphincter stents, airway stents, tracheobronchial stents, trachealstents, laryngeal stents, esophageal stents, single stents, segmentedstents, joined stents, overlap stents, tapered stents, and bifurcatedstents.

When the device is a stent, the stent can have any pattern and designsuitable for its intended use. The stent can be implanted in a subjectfor treatment of a wide variety of conditions, including obstruction ornarrowing of a vessel (e.g., blood vessel) or other tubular tissue ororgan in the body. In certain embodiments, the biodegradable stentexhibits a percentage radially inward recoil of about 20% or less, or ofabout 15% or less, or of about 10% or less, or of about 8% or less, orof about 6% or less, upon deployment or after deployment of the stent,or at any time ranging from about day 0 to about day 30 after deploymentin aqueous condition at about 37° C. in vitro or in vivo. In anembodiment, the stent exhibits percent recoil of about 10% or less afterdeployment, or after radial expansion in aqueous condition at about 37°C. in vitro or in vivo.

The stents can have any pattern and design suitable for their intendeduse. For example, the stents can comprise serpentine rings connected toone another directly or via links, have open cells or closed cells,comprise helical ring(s), comprise coil(s), comprise corrugated rings,have a slide-and-lock design, be a slotted tube, be a rolled sheet, or acombination thereof. Furthermore, the stents can have supportingfeatures, as described in U.S. patent application Ser. No. 12/016,077and U.S. Provisional Patent Application No. 60/885,700, the fulldisclosure of each of which is incorporated herein by reference.Moreover, the stents can have openings in the struts, crowns and/orlinks, as described in U.S. 60/885,700.

To help determine the position of a stent in the body of a subject, thestent can have a radiopaque marker at any suitable position, e.g., atthe proximal end and the distal end of the stent, and optionally in anintermediate portion of the stent. Alternatively or in addition, thebody of the stent or a layer of the body, and/or a coating on the stent,can contain a radiopaque agent or material.

In some embodiments, biodegradable implantable devices havesubstantially W-shaped cells. In certain embodiments, stents havingsubstantially W-shaped cells have the stent pattern shown in FIG. 1 or asubstantially similar pattern. The stent pattern in FIG. 1 is in an “ascut” state.

The stent pattern in FIG. 1 comprises a plurality of intermediatecylindrical rings between the cylindrical ring at the proximal end andthe cylindrical ring at the distal end of the stent, each cylindricalring comprising a plurality of struts and a plurality of crownsconnecting immediately adjacent struts which form a substantiallysinusoidal pattern of alternating peaks and troughs, wherein immediatelyadjacent intermediate cylindrical rings are connected to one another atcrowns via a plurality of links, and wherein:

immediately adjacent intermediate cylindrical rings and links define aplurality of substantially W-shaped cells;

each substantially W-shaped cell not immediately adjacent to thecylindrical ring at the proximal or distal end abuts six othersubstantially W-shaped cells; and

the perimeter of each substantially W-shaped cell includes 8 struts, 10crowns and 2 links.

In some embodiments, each substantially W-shaped cell immediatelyadjacent to the cylindrical ring at the proximal end of the stent,and/or each substantially W-shaped cell immediately adjacent to thecylindrical ring at the distal end, does not abut six othersubstantially W-shaped cells. In certain embodiments, none of thesubstantially W-shaped cells immediately adjacent to the cylindricalring at the proximal end of the stent, and/or none of the substantiallyW-shaped cells immediately adjacent to the cylindrical ring at thedistal end, abuts six other substantially W-shaped cells.

In the stent pattern of FIG. 1, the links connecting immediatelyadjacent intermediate cylindrical rings are substantially parallel tothe longitudinal axis of the stent. In other embodiments, the links areoriented at an angle (e.g., about 1 degree to about 45 degrees, or about5 degrees to about 35 degrees, or about 10 degrees to about 25 degrees)relative to the longitudinal axis of the stent.

In FIG. 1, crowns of an intermediate cylindrical ring which are notconnected to a crown of an immediately adjacent intermediate cylindricalring via a link are substantially curved, except that certain crowns ofthe intermediate cylindrical ring immediately adjacent to the proximalend and certain crowns of the intermediate cylindrical ring immediatelyadjacent to the distal end which are not connected to a crown of therespective immediately adjacent intermediate cylindrical ring via a linkare substantially flat. Crowns of an intermediate cylindrical ring whichare connected to a crown of an immediately adjacent intermediatecylindrical ring via a link are substantially flat. In otherembodiments, crowns of an intermediate cylindrical ring which are notconnected to a crown of an immediately adjacent intermediate cylindricalring via a link are substantially flat, and crowns of an intermediatecylindrical ring which are connected to a crown of an immediatelyadjacent intermediate cylindrical ring via a link are substantiallycurved. In yet other embodiments, all crowns of intermediate cylindricalrings are substantially curved. In still other embodiments, all crownsof intermediate cylindrical rings are substantially flat.

In certain embodiments, immediately adjacent struts of intermediatecylindrical rings are oriented relative to one another at an interiorangle of about 90 degrees to about 150 degrees, or about 100 degrees toabout 140 degrees, or about 110 degrees to about 130 degrees, when thestent is in a non-deformed configuration (e.g., the as cut state). In anembodiment, immediately adjacent struts of intermediate cylindricalrings are oriented relative to one another at an interior angle of about120 degrees when the stent is in a non-deformed configuration (e.g., theas cut state). In some embodiments, the interior angle of immediatelyadjacent struts connected by a substantially curved crown issubstantially similar to the interior angle of immediately adjacentstruts connected by a substantially flat crown when the stent is in anon-deformed configuration (e.g., the as cut state) or in a deformedconfiguration (e.g., crimped or radially expanded).

In the stent pattern of FIG. 1, immediately adjacent intermediatecylindrical rings are substantially in-phase of one another. In otherembodiments, opposing peaks of immediately adjacent intermediatecylindrical rings are circumferentially offset from one another,opposing troughs of immediately adjacent intermediate cylindrical ringsare circumferentially offset from one another, and opposing peaks andtroughs of immediately adjacent intermediate cylindrical rings arecircumferentially offset from one another. In certain embodiments,immediately adjacent intermediate cylindrical rings are substantiallycompletely out-of-phase of one another, where opposing peaks and troughsof immediately adjacent intermediate cylindrical rings are substantiallycircumferentially aligned.

In FIG. 1, immediately adjacent intermediate cylindrical rings areconnected to one another via a plurality of peak-to-peak links. In otherembodiments, immediately adjacent intermediate cylindrical rings areconnected to one another via a plurality of trough-to-trough links. Inyet other embodiments, immediately adjacent intermediate cylindricalrings are connected to one another via a plurality of peak-to-troughlinks, or via a plurality of trough-to-peak links.

In the stent pattern of FIG. 1, links connecting a pair of immediatelyadjacent intermediate cylindrical rings are circumferentially offset bytwo crowns from circumferentially adjacent links connecting animmediately adjacent pair of immediately adjacent intermediatecylindrical rings. In other embodiments, links connecting a pair ofimmediately adjacent intermediate cylindrical rings arecircumferentially offset by one crown, or three crowns, or four crowns,or more crowns from circumferentially adjacent links connecting animmediately adjacent pair of immediately adjacent intermediatecylindrical rings. In still other embodiments, links connecting a pairof immediately adjacent intermediate cylindrical rings are substantiallynot circumferentially offset from circumferentially adjacent linksconnecting an immediately adjacent pair of immediately adjacentintermediate cylindrical rings.

In FIG. 1, immediately adjacent intermediate cylindrical rings have 16crowns (8 peaks and 8 troughs) and are connected to one another via 4links to form 4 substantially W-shaped cells. In other embodiments,immediately adjacent intermediate cylindrical rings have 8 crowns (4peaks and 4 troughs) and are connected to one another via 2 links toform 2 substantially W-shaped cells. In yet other embodiments,immediately adjacent intermediate cylindrical rings have 12 crowns (6peaks and 6 troughs) and are connected to one another via 3 links toform 3 substantially W-shaped cells. In further embodiments, immediatelyadjacent intermediate cylindrical rings have 20 crowns (10 peaks and 10troughs) and are connected to one another via 5 links to form 5substantially W-shaped cells. In still further embodiments, immediatelyadjacent intermediate cylindrical rings have 24 crowns (12 peaks and 12troughs) and are connected to one another via 6 links to form 6substantially W-shaped cells. The present disclosure also encompassesembodiments where immediately adjacent intermediate cylindrical ringshaving, e.g., 16 crowns (8 peaks and 8 troughs) are connected to oneanother via a plurality of links other than 4 links (e.g., via 2, 3, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16 links), in which case the ringsand links connecting them may form or may not form substantiallyW-shaped cells.

The cylindrical ring at the proximal end of the stent is connected tothe intermediate cylindrical ring immediately adjacent thereto at crownsvia a plurality of links, and the cylindrical ring at the distal end isconnected to the intermediate cylindrical ring immediately adjacentthereto at crowns via a plurality of links.

In the stent pattern of FIG. 1, the links connecting the cylindricalring at the proximal end to the intermediate cylindrical ringimmediately adjacent thereto are substantially parallel to thelongitudinal axis of the stent, and the links connecting the cylindricalring at the distal end to the intermediate cylindrical ring immediatelyadjacent thereto are substantially parallel to the longitudinal axis ofthe stent. In other embodiments, the links connecting the cylindricalring at the proximal end to the intermediate cylindrical ringimmediately adjacent thereto are oriented at an angle (e.g., about 1degree to about 45 degrees, or about 5 degrees to about 35 degrees, orabout 10 degrees to about 25 degrees) relative to the longitudinal axisof the stent, and/or the links connecting the cylindrical ring at thedistal end to the intermediate cylindrical ring immediately adjacentthereto are oriented at an angle (e.g., about 1 degree to about 45degrees, or about 5 degrees to about 35 degrees, or about 10 degrees toabout 25 degrees) relative to the longitudinal axis of the stent.

In FIG. 1, crowns of the cylindrical ring at the proximal end which arenot connected to a crown of the intermediate cylindrical ringimmediately adjacent thereto via a link are substantially flat, andcrowns of the cylindrical ring at the proximal end which are connectedto a crown of the intermediate cylindrical ring immediately adjacentthereto via a link are substantially curved. In other embodiments,crowns of the cylindrical ring at the proximal end which are notconnected to a crown of the intermediate cylindrical ring immediatelyadjacent thereto via a link are substantially curved, and crowns of thecylindrical ring at the proximal end which are connected to a crown ofthe intermediate cylindrical ring immediately adjacent thereto via alink are substantially flat. In yet other embodiments, all crowns of thecylindrical ring at the proximal end are substantially curved. In stillother embodiments, all crowns of the cylindrical ring at the proximalend are substantially flat.

Also in FIG. 1, crowns of the cylindrical ring at the distal end whichare not connected to a crown of the intermediate cylindrical ringimmediately adjacent thereto via a link are substantially curved, andcrowns of the cylindrical ring at the distal end which are connected toa crown of the intermediate cylindrical ring immediately adjacentthereto via a link are substantially flat. In other embodiments, crownsof the cylindrical ring at the distal end which are not connected to acrown of the intermediate cylindrical ring immediately adjacent theretovia a link are substantially flat, and crowns of the cylindrical ring atthe distal end which are connected to a crown of the intermediatecylindrical ring immediately adjacent thereto via a link aresubstantially curved. In yet other embodiments, all crowns of thecylindrical ring at the distal end are substantially curved. In stillother embodiments, all crowns of the cylindrical ring at the distal endare substantially flat.

In certain embodiments, immediately adjacent struts of the cylindricalrings at the proximal and distal ends of the stent are oriented relativeto one another at an interior angle of about 90 degrees to about 150degrees, or about 100 degrees to about 140 degrees, or about 110 degreesto about 130 degrees, when the stent is in a non-deformed configuration(e.g., the as cut state). In an embodiment, immediately adjacent strutsof the cylindrical rings at the proximal and distal ends are orientedrelative to one another at an interior angle of about 120 degrees whenthe stent is in a non-deformed configuration (e.g., the as cut state).For the cylindrical rings at the proximal and distal ends, in someembodiments the interior angle of immediately adjacent struts connectedby a substantially curved crown is substantially similar to the interiorangle of immediately adjacent struts connected by a substantially flatcrown when the stent is in a non-deformed configuration (e.g., the ascut state) or in a deformed configuration (e.g., crimped or radiallyexpanded).

In the stent pattern of FIG. 1, the cylindrical rings at the proximaland distal ends and the respective immediately adjacent intermediatecylindrical ring are substantially completely out-of-phase of oneanother. In other embodiments, opposing peaks, opposing troughs, andopposing peaks and troughs of the cylindrical ring at the proximal end,and/or the cylindrical ring at the distal end, and the respectiveimmediately adjacent intermediate cylindrical ring are circumferentiallyoffset from one another. In still other embodiments, the cylindricalring at the proximal end, and/or the cylindrical ring at the distal end,and the respective immediately adjacent intermediate cylindrical ringare substantially in-phase of one another.

In FIG. 1, the cylindrical rings at the proximal and distal ends of thestent and the respective immediately adjacent intermediate cylindricalring are connected to one another via a plurality of peak-to-troughlinks. In other embodiments, the cylindrical ring at the proximal end,and/or the cylindrical ring at the distal end, and the respectiveimmediately adjacent intermediate cylindrical ring are connected to oneanother via a plurality of trough-to-peak links, or peak-to-peak links,or trough-to-trough links.

Also in FIG. 1, links connecting the cylindrical ring at the proximalend and the intermediate cylindrical ring immediately adjacent theretoare circumferentially offset by one crown from circumferentiallyadjacent links connecting the cylindrical ring at the distal end and theintermediate cylindrical ring immediately adjacent thereto. In otherembodiments, links connecting the cylindrical ring at the proximal endand the intermediate cylindrical ring immediately adjacent thereto arecircumferentially offset by two crowns, or three crowns, or four crowns,or more crowns from circumferentially adjacent links connecting thecylindrical ring at the distal end and the intermediate cylindrical ringimmediately adjacent thereto. In yet other embodiments, links connectingthe cylindrical ring at the proximal end and the intermediatecylindrical ring immediately adjacent thereto are substantially notcircumferentially offset from circumferentially adjacent linksconnecting the cylindrical ring at the distal end and the intermediatecylindrical ring immediately adjacent thereto.

In the stent pattern of FIG. 1, the cylindrical ring at the proximal endand the intermediate cylindrical ring immediately adjacent thereto areconnected to one another via 8 links and form 8 non-W-shaped cells. Inother embodiments, the cylindrical ring at the proximal end and theintermediate cylindrical ring immediately adjacent thereto are connectedto one another via 2, 3, 4, 5, 6, 7, 9, 10 or more links and form one ormore non-W-shaped cells and/or one or more substantially W-shaped cells.Also in FIG. 1, the cylindrical ring at the distal end and theintermediate cylindrical ring immediately adjacent thereto are connectedto one another via 8 links and form 8 non-W-shaped cells. In otherembodiments, the cylindrical ring at the distal end and the intermediatecylindrical ring immediately adjacent thereto are connected to oneanother via 2, 3, 4, 5, 6, 7, 9, 10 or more links and form one or morenon-W-shaped cells and/or one or more substantially W-shaped cells.

In FIG. 1, the cylindrical rings at the proximal and distal ends of thestent have 16 crowns (8 peaks and 8 troughs). The cylindrical rings atthe proximal and distal ends can also have any number of crowns rangingfrom 8 crowns (4 peaks and 4 troughs) to 24 crowns (12 peaks and 12troughs), or from 12 crowns (6 peaks and 6 troughs) to 20 crowns (10peaks and 10 troughs).

In some embodiments, at least one (e.g., one, two or more) of the linksconnecting the cylindrical ring at the proximal end and the intermediatecylindrical ring immediately adjacent thereto is a marker linkcomprising at least one opening for containing a radiopaque marker, andat least one (e.g., one, two or more) of the links connecting thecylindrical ring at the distal end and the intermediate cylindrical ringimmediately adjacent thereto is a marker link comprising at least oneopening for containing a radiopaque marker. In additional embodiments,at least one (e.g., one, two or more) of the links connectingimmediately adjacent intermediate cylindrical rings is a marker linkcomprising at least one opening for containing a radiopaque marker.

The radiopaque marker can comprise any suitable radiopaque material.Examples of radiopaque material include without limitation gold,magnesium, platinum, platinum-iridium alloys (e.g., those containing atleast about 1%, 5%, 10%, 20% or 30% iridium), tantalum, tungsten, andalloys thereof. The radiopaque marker can have any suitable form (e.g.,particle or bead).

In certain embodiments, the at least one marker link at the proximalend, the at least one marker link at the distal end, and optionally atleast one marker link connecting immediately adjacent intermediatecylindrical rings each comprise two openings for containing a radiopaquemarker. In some embodiments, the two openings of the at least one markerlink at the proximal end are substantially transverse to the axis of thelink, the two openings of the at least one marker link at the distal endare substantially transverse to the axis of the link, and/or the twoopenings of the optional at least one marker link connecting immediatelyadjacent intermediate cylindrical rings are substantially transverse tothe axis of the link. In other embodiments, the two openings of the atleast one marker link at the proximal end are along the axis of thelink, the two openings of the at least one marker link at the distal endare along the axis of the link, and/or the two openings of the optionalat least one marker link connecting immediately adjacent intermediatecylindrical rings are along the axis of the link.

In some embodiments, the struts and crowns of the cylindrical rings havea substantially squarish, substantially rectangular, substantiallycircular or substantially oval cross-section. In certain embodiments,the struts and crowns of the cylindrical rings independently have athickness (e.g., average thickness) of about 0.003 inch (about 76microns) to about 0.01 inch (about 254 microns), or about 0.004 inch(about 102 microns) to about 0.008 inch (about 203 microns), or about0.005 inch (about 127 microns) to about 0.007 inch (about 178 microns),and a width (e.g., average width) of about 0.003 inch (about 76 microns)to about 0.012 inch (about 305 microns), or about 0.005 inch (about 127microns) to about 0.01 inch (about 254 microns), or about 0.004 inch(about 102 microns) to about 0.008 inch (about 203 microns). In someembodiments, the struts and crowns of the cylindrical ringsindependently have a thickness (e.g., average thickness) of about 0.004inch (about 102 microns) to about 0.008 inch (about 203 microns), and awidth (e.g., average width) of about 0.004 inch (about 102 microns) toabout 0.008 inch (about 203 microns). In an embodiment, the struts andcrowns of the cylindrical rings have an average thickness of about 0.006inch (about 152 microns) and an average width of about 0.0065 inch(about 165 microns).

In other embodiments, the struts and crowns of the cylindrical ringshave a substantially trapezoidal cross-section. In certain embodiments,the struts and crowns of the cylindrical rings independently have athickness (e.g., average thickness) of about 0.003 inch (about 76microns) to about 0.01 inch (about 254 microns), or about 0.004 inch(about 102 microns) to about 0.008 inch (about 203 microns), or about0.005 inch (about 127 microns) to about 0.007 inch (about 178 microns),an outer (abluminal) width (e.g., average abluminal width) of about0.003 inch (about 76 microns) to about 0.009 inch (about 229 microns),or about 0.004 inch (about 102 microns) to about 0.008 inch (about 203microns), or about 0.005 inch (about 127 microns) to about 0.007 inch(about 178 microns), and an inner (luminal) width (e.g., average luminalwidth) of about 0.004 inch (about 102 microns) to about 0.012 inch(about 305 microns), or about 0.005 inch (about 127 microns) to about0.01 inch (about 254 microns), or about 0.006 inch (about 152 microns)to about 0.009 inch (about 229 microns). In some embodiments, the strutsand crowns of the cylindrical rings independently have a thickness(e.g., average thickness) of about 0.004 inch (about 102 microns) toabout 0.008 inch (about 203 microns), an abluminal width (e.g., averageabluminal width) of about 0.004 inch (about 102 microns) to about 0.008inch (about 203 microns), and a luminal width (e.g., average luminalwidth) of about 0.005 inch (about 127 microns) to about 0.01 inch (about254 microns). The outer (abluminal) width of the struts of thecylindrical rings can be greater or less than the inner (luminal) widthof the struts, and the abluminal width of the crowns of the cylindricalrings can also be greater or less than the luminal width of the crowns.In some embodiments, the outer (abluminal) width of the struts andcrowns of the cylindrical rings is less than the inner (luminal) widthof the struts and crowns for better penetration of the struts and crownsinto the wall of a treated vessel. In an embodiment, the struts andcrowns of the cylindrical rings have an average thickness of about 0.006inch (about 152 microns), an average outer (abluminal) width of about0.006 inch (about 152 microns), and an average inner (luminal) width ofabout 0.0075 inch (about 190 microns).

In some embodiments, the struts of the cylindrical rings have asubstantially similar cross-section, a substantially similar thicknessand substantially similar width(s) as the crowns of the cylindricalrings. In other embodiments, the struts of the cylindrical rings have adifferent cross-section, a different thickness (greater or smaller),and/or different width(s) (greater or smaller) than the crowns of thecylindrical rings.

In further embodiments, the struts and crowns of the intermediatecylindrical rings have a substantially similar cross-section, asubstantially similar thickness and substantially similar width(s) asthe struts and crowns of the cylindrical rings at the proximal anddistal ends of the stent. In other embodiments, the struts and crowns ofthe intermediate cylindrical rings have a different cross-section, adifferent thickness (greater or smaller), and/or different width(s)(greater or smaller) than the struts and crowns of the cylindrical ringsat the proximal and distal ends.

In additional embodiments, the struts of the cylindrical rings have alength (e.g., average length) of about 0.005 inch (about 127 microns) toabout 0.025 inch (about 635 microns), or about 0.01 inch (about 254microns) to about 0.02 inch (about 508 microns). In an embodiment, thestruts of the cylindrical rings have an average length of about 0.015inch (about 381 microns). In certain embodiments, the struts of theintermediate cylindrical rings have a substantially similar length asthe struts of the cylindrical rings at the proximal and distal ends ofthe stent. In other embodiments, the struts of the intermediatecylindrical rings have a different length (longer or shorter) than thestruts of the cylindrical rings at the proximal and distal ends.

In further embodiments, the substantially flat crowns of the cylindricalrings have a length (e.g., average length) of about 0.002 inch (about 51microns) to about 0.02 inch (about 508 microns), or about 0.006 inch(about 152 microns) to about 0.016 inch (about 406 microns). In anembodiment, the substantially flat crowns of the cylindrical rings havean average length of about 0.011 inch (about 279 microns). In someembodiments, the substantially flat crowns of the intermediatecylindrical rings have a substantially similar length as thesubstantially flat crowns of the cylindrical rings at the proximal anddistal ends of the stent. In other embodiments, the substantially flatcrowns of the intermediate cylindrical rings have a different length(longer or shorter) than the substantially flat crowns of thecylindrical rings at the proximal and distal ends.

In some embodiments, the links connecting immediately adjacentcylindrical rings have a substantially squarish, substantiallyrectangular, substantially circular or substantially oval cross-section.In certain embodiments, the links connecting immediately adjacentcylindrical rings have a thickness (e.g., average thickness) of about0.003 inch (about 76 microns) to about 0.01 inch (about 254 microns), orabout 0.004 inch (about 102 microns) to about 0.008 inch (about 203microns), or about 0.005 inch (about 127 microns) to about 0.007 inch(about 178 microns), and a width (e.g., average width) of about 0.002inch (about 51 microns) to about 0.008 inch (about 203 microns), orabout 0.002 inch (about 51 microns) to about 0.006 inch (about 152microns), or about 0.003 inch (about 76 microns) to about 0.005 inch(about 127 microns). In some embodiments, the links have a thickness(e.g., average thickness) of about 0.004 inch (about 102 microns) toabout 0.008 inch (about 203 microns), and a width (e.g., average width)of about 0.002 inch (about 51 microns) to about 0.006 inch (about 152microns). In an embodiment, the links have an average thickness of about0.006 inch (about 152 microns) and an average width of about 0.004 inch(about 102 microns).

In other embodiments, the links connecting immediately adjacentcylindrical rings have a substantially trapezoidal cross-section. Incertain embodiments, the links connecting immediately adjacentcylindrical rings have a thickness (e.g., average thickness) of about0.003 inch (about 76 microns) to about 0.01 inch (about 254 microns), orabout 0.004 inch (about 102 microns) to about 0.008 inch (about 203microns), or about 0.005 inch (about 127 microns) to about 0.007 inch(about 178 microns), an outer (abluminal) width (e.g., average abluminalwidth) of about 0.002 inch (about 51 microns) to about 0.006 inch (about152 microns), or about 0.002 inch (about 51 microns) to about 0.005 inch(about 127 microns), or about 0.003 inch (about 76 microns) to about0.005 inch (about 127 microns), and an inner (luminal) width (e.g.,average luminal width) of about 0.002 inch (about 51 microns) to about0.008 inch (about 203 microns), or about 0.003 inch (about 76 microns)to about 0.006 inch (about 152 microns), or about 0.003 inch (about 76microns) to about 0.005 inch (about 127 microns). In some embodiments,the links have a thickness (e.g., average thickness) of about 0.004 inch(about 102 microns) to about 0.008 inch (about 203 microns), anabluminal width (e.g., average abluminal width) of about 0.002 inch(about 51 microns) to about 0.005 inch (about 127 microns), and aluminal width (e.g., average luminal width) of about 0.003 inch (about76 microns) to about 0.006 inch (about 152 microns). The outer(abluminal) width of the links can be greater or less than their inner(luminal) width. In some embodiments, the abluminal width of the linksis less than their luminal width. In an embodiment, the links connectingimmediately adjacent cylindrical rings have an average thickness ofabout 0.006 inch (about 152 microns), an average outer (abluminal) widthof about 0.0035 inch (about 89 microns), and an average inner (luminal)width of about 0.0045 inch (about 114 microns).

In some embodiments, the links connecting immediately adjacentcylindrical rings have a substantially similar thickness as the strutsand/or the crowns of the cylindrical rings. In other embodiments, thelinks have a thickness greater or less than the thickness of the strutsand/or the crowns of the cylindrical rings. The links connectingimmediately adjacent cylindrical rings can also have width(s)substantially similar to, or greater or less than, the width(s) of thestruts and/or the crowns of the cylindrical rings. In certainembodiments, the links have width(s) less than the width(s) of thestruts/or the crowns of the cylindrical rings.

In further embodiments, the links connecting the cylindrical ring at theproximal end and the intermediate cylindrical ring immediately adjacentthereto and the links connecting the cylindrical ring at the distal endand the intermediate cylindrical ring immediately adjacent thereto havea substantially similar cross-section, a substantially similar thicknessand substantially similar width(s) as the links connecting immediatelyadjacent intermediate cylindrical rings. In other embodiments, the linksconnecting the cylindrical ring at the proximal end and the intermediatecylindrical ring immediately adjacent thereto and/or the linksconnecting the cylindrical ring at the distal end and the intermediatecylindrical ring immediately adjacent thereto have a differentcross-section, a different thickness (greater or smaller), and/ordifferent width(s) (greater or smaller) than the links connectingimmediately adjacent intermediate cylindrical rings.

In additional embodiments, the marker links at the proximal and distalends, and optional marker link(s) in intermediate portion(s) of thestent, have a substantially similar cross-section, a substantiallysimilar thickness and substantially similar width(s) as the non-markerlinks at the proximal end, the distal end and intermediate portions. Inother embodiments, the marker links at the proximal end, the distal endand/or intermediate portion(s) of the stent have a differentcross-section, a different thickness (greater or smaller), and/ordifferent width(s) (greater or smaller) than the non-marker links at theproximal end, the distal end and/or intermediate portions. In certainembodiments, the marker links at the proximal end, the distal end and/orintermediate portion(s) of the stent have a greater width than thenon-marker links at the proximal end, the distal end and/or intermediateportions, e.g., when the marker links comprise one or more openings forcontaining radiopaque markers along the axis of the links.

In certain embodiments, the links connecting immediately adjacentcylindrical rings have a length (e.g., average length) of about 0.01inch (about 254 microns) to about 0.035 inch (about 889 microns), orabout 0.015 inch (about 381 microns) to about 0.03 inch (about 762microns). In an embodiment, the links have an average length of about0.0225 inch (about 572 microns). In some embodiments, the linksconnecting the cylindrical ring at the proximal end and the intermediatecylindrical ring immediately adjacent thereto and the links connectingthe cylindrical ring at the distal end and the intermediate cylindricalring immediately adjacent thereto have a substantially similar length asthe links connecting immediately adjacent intermediate cylindricalrings. In other embodiments, the links connecting the cylindrical ringat the proximal end and the intermediate cylindrical ring immediatelyadjacent thereto and the links connecting the cylindrical ring at thedistal end and the intermediate cylindrical ring immediately adjacentthereto have a different length (longer or shorter) than the linksconnecting immediately adjacent intermediate cylindrical rings (e.g.,the links at the proximal and distal ends may have a longer length whenthe marker links at the proximal and distal ends comprise one or moreopenings for containing radiopaque markers along the axis of the links).

The links connecting immediately adjacent cylindrical rings can have alength substantially similar to, or greater or less than, the length ofthe struts of the cylindrical rings. In certain embodiments, the lengthof the links is greater than the length of the struts.

In further embodiments, the curvilinear length (e.g., averagecurvilinear length) of a substantially W-shaped cell is about 0.02 inch(about 0.5 mm) to about 0.2 inch (about 5.1 mm), or about 0.05 inch(about 1.3 mm) to about 0.15 inch (about 3.8 mm) In an embodiment, theaverage curvilinear length of a substantially W-shaped cell is about 0.1inch (about 2.5 mm) If the proximal end and/or the distal end of thestent have substantially W-shaped cells, the curvilinear length of asubstantially W-shaped cell at the proximal end and/or the distal endcan be substantially similar to, or greater or less than, thecurvilinear length of a substantially W-shaped cell in an intermediateportion of the stent.

In additional embodiments, the curvilinear length (e.g., averagecurvilinear length) of a cylindrical ring is about 0.2 inch (about 5.1mm) to about 0.6 inch (about 15.2 mm), or about 0.3 inch (about 7.6 mm)to about 0.5 inch (about 12.7 mm) In an embodiment, the averagecurvilinear length of a cylindrical ring is about 0.41 inch (about 10.4mm) The cylindrical rings at the proximal and distal ends and theintermediate cylindrical rings can have a curvilinear lengthsubstantially similar to one another or different (greater or less) thanone another. In certain embodiments, the curvilinear length of thecylindrical rings at the proximal and distal ends is substantiallysimilar to the curvilinear length of the intermediate cylindrical rings.

A stent having the pattern of FIG. 1 or a substantially similar patterncan have any length suitable for its intended use. In some embodiments,the length of the stent is about 5 mm to about 40 mm, or about 10 mm toabout 30 mm, or about 10 mm to about 20 mm, or about 10 mm to about 18mm, or about 12 mm to about 16 mm, or about 13 mm to about 15 mm, orabout 13 mm to about 14 mm, when the stent is in a non-deformedconfiguration (e.g., the as cut state) or in a deformed configuration(e.g., crimped or radially expanded). In certain embodiments, the lengthof the stent is about 10 mm to about 20 mm when the stent is in anon-deformed configuration (e.g., the as cut state) or in a deformedconfiguration (e.g., crimped or radially expanded). In certainembodiments, the length of the stent is about 13.3 or 13.5 mm when thestent is in a non-deformed configuration (e.g., the as cut state).

The number of cylindrical rings that a stent has may depend on variousfactors, including the length of the stent. In some embodiments, a stenthaving a length of about 10 mm to about 20 mm has about 10 to about 35cylindrical rings, or about 12 to about 30 cylindrical rings, or about13 to about 26 cylindrical rings, or about 15 to about 22 cylindricalrings. In certain embodiments, a stent having a length of about 10 mm toabout 20 mm has about 13 to about 26 cylindrical rings. In furtherembodiments, a stent having a length of about 12 mm to about 16 mm hasabout 11 to about 28 cylindrical rings, or about 13 to about 25cylindrical rings, or about 15 to about 21 cylindrical rings. In certainembodiments, a stent having a length of about 12 mm to about 16 mm hasabout 15 to about 21 cylindrical rings. In additional embodiments, astent having a length of about 13.3 or 13.5 mm has about 17 cylindricalrings.

The following examples are provided merely to illustrate the presentdisclosure and are not intended to limit the scope of the disclosure.

Example 1 Stent Fabrication

A. Patterning and Coating a Stent

A 14 mm stent having a selected pattern (e.g., that of FIG. 1) was cutfrom a polymeric tube using a laser. The outer diameter (OD) of thestent was about 0.142 inch, and the thickness of the struts, crowns andlinks of the stent was about 0.006 inch. A solution containing apolymer, e.g., 85:15 poly(L-lactide-co-glycolide), and a drug (e.g.,myolimus) in a weight ratio of about 3:2 and at a combined concentrationof about 1.7 mg/mL in a solvent (e.g., dichloromethane) was sprayed ontothe stent to form a coating on the stent containing a wet weight of thepolymer and the drug of about 270 μg. The stent was put under vacuum atambient temperature for at least 36 hours to remove, e.g., any residualsolvent, yielding a dryer coating weight of about 130-150 μg. The coatedstent was then heated at 70° C. for 15 minutes to stabilize the coatingon the stent and remove any additional residual solvent, yielding acoating weight of about 125-135 μg. The average thickness of the coatingwas less than 5 microns.

B. Sterilizing the Stent

The stent delivery system (crimped stent mounted onto theballoon-catheter) was packaged in a pouch and sterilized by exposure toe-beam radiation (30 kGy total dose with the stent being exposed to aninternal dose of about 22.5 kGy).

C. Physical Properties of the Stent

Physical properties of stents (having the pattern of FIG. 1) andpolymeric tubes made of poly(L-lactide) (PLLA) homopolymer or one ofvarious poly(L-lactide-co-ε-caprolactone) [poly(LLA-co-CL)] copolymerswere measured. Radial strength, stiffness and % recoil of uncoatedstents were measured after the stents were heated at 70° C. for 15minutes and crimped without sterilization or after the stents wereheated at 70° C. for 15 minutes, crimped and then sterilized. The %crystallinity, glass transition temperature (T_(g)), crystallizationenthalpy (ΔH_(c)) and melting enthalpy (ΔH_(m)) of the polymericmaterial composing a tube having no coating were measured after the tubewas heated at 70° C. for 15 minutes without sterilization or after thetube was heated at 70° C. for 15 minutes and then sterilized.

Percent recoil was measured according to the procedures described in theASTM F 2079-09 document entitled “Standard Test Method for MeasuringIntrinsic Elastic Recoil of Balloon-Expandable Stents”. Radial strengthand stiffness were measured according to the procedures described in thedraft ASTM WK15227 document entitled “Standard Practice/Guide forMeasuring Radial Strength of Balloon-Expandable and Self-ExpandableVascular Stents”, adapted such that the stent was characterized underphysiological conditions. The T_(g), crystallization enthalpy andmelting enthalpy were measured according to the procedures described inthe ASTM D3418-08 document entitled “Standard Test Method for TransitionTemperatures and Enthalpies of Fusion and Crystallization of Polymers byDifferential Scanning calorimetry”. H. Qin et al., Macromolecules,37:5239-5249 (2004) also discuss crystallization enthalpies during firstheating and first cooling.

Percent crystallinity by weight was measured by X-ray diffraction (XRD).Briefly, a sample was flattened in a die and hydraulic press prior tomeasurement and then was placed on a zero-background silicon sampleholder. Scans were run on a Panalytical X'pert MPD Pro diffractometerusing copper radiation at 45 KV/40 mA and covering the range of 5degrees to 70 degrees with a step size of 0.02 degree and a countingtime of 500 seconds per step.

Results of the measurements are shown in Table 2 below. Sterilizationwith e-beam had a greater effect on the % crystallinity of the polymericmaterial [90:10 poly(LLA-co-CL) or 95:5 poly(LLA-co-CL)] composing apolymeric tube than on its T_(g). The stents made of 70:30poly(LLA-co-CL) or 85:15 poly(LLA-co-CL) exhibited the lowest radialstrength and stiffness. Without intending to be bound by theory, apossible reason for the low recoil of the stents made of 70:30poly(LLA-co-CL) or 85:15 poly(LLA-co-CL) is that those stents may have agreater self-expandable character and hence may have an enhancedtendency to expand to the larger diameter of the polymeric tube fromwhich the stent was cut.

TABLE 2 Properties of polymeric tubes and stents made of poly(L-lactide)or a poly(L-lactide-co-ε-caprolactone) copolymer Polymer Radial (MolarStrength Stiffness Percent ΔH_(c), 1^(st) ΔH_(c), 1^(st) SterilizedRatio of % Recoil at 37° C. at 37° C. Crystallinity _(g) (° C.) HeatingCooling H_(m) with E- LLA:CL) at 37° C. (psi) (N/mm²) (by wt) (Dry)(J/g) (J/g) (J/g) Beam? 100% 8.5% 10.3 0.6 21.6% 3.3 0.9 28.8 7.7 YesPLLA 95:5 6.6% 14.1 0.9 21.3% 8.6 1.5 3.8 4.3 Yes poly(LLA- co-CL) 95:56.1% 16.9 0.9 18.2% 5.3 0.0 0.0 0.5 No poly(LLA- co-CL) 90:10 5.2% 18.41.3 15.0% 9.9 0.0 0.0 0.6 Yes poly(LLA- co-CL) 90:10 4.9% 20.8 1.2 8.3%9.2 0.0 0.0 5.5 No poly(LLA- co-CL) 85:15 4.9% 5.3 0.3 6.3% 7.9 0.0 2.0Yes poly(LLA- co-CL) 70:30 5.1% 6.5 0.4 5.8% 9.8 1.4 2.7 Yes poly(LLA-co-CL)

Physical properties of stents (having the pattern of FIG. 1) composed ofa blend of poly(L-lactide-co-ε-caprolactone) [poly(LLA-co-CL)]copolymers having various L-lactide and caprolactone molar ratios(70:30, 85:15 or 95:5) were also measured. The stents were made usingprocedures substantially similar to those described in this Example.Radial strength, stiffness and % recoil of uncoated stents were measuredafter the stents were heated at 70° C. for 15 minutes (the step forstabilizing a coating on a stent in this Example), crimped and thensterilized with e-beam radiation. The results are shown in Table 3.

TABLE 3 Physical properties of stents composed of a blend ofpoly(LLA-co-CL) copolymers Radial Strength Stiffness Composition ofStent (psi) (N/mm²) % Recoil 40:60 (w/w) 95:5 poly(LLA-co-CL) + 15.9 1.14% 85:15 poly(LLA-co-CL) 50:50 (w/w) 95:5 poly(LLA-co-CL) + 17.0 1.1 6%85:15 poly(LLA-co-CL) 75:25 (w/w) 95:5 poly(LLA-co-CL) + 14.1 0.8 6%70:30 poly(LLA-co-CL) 90:10 (w/w) 95:5 poly(LLA-co-CL) + 15.8 1.0 5%70:30 poly(LLA-co-CL)

D. Compositions of Polymeric Tubes and Coatings

Using procedures substantially similar to those described above in thisExample, polymeric tubes having a variety of compositions (e.g.,polymers, drugs and/or additives; see Table 4) were made and coatingscontaining various compositions (see Table 5) were applied to stents cutfrom polymeric tubes.

TABLE 4 Compositions of polymeric tubes P + A or P:A or P:D P + D RatioConc'n in (w/w) in Spray Solvent Polymer (P) Additive (A) Drug (D)Solvent Solvent (mg/mL) 85:15 poly(LLA-co-GA) none none DCM 7 90:10poly(LLA-co-TMC) none none DCM 10 95:5 poly(LLA-co-CL) none none 90:10poly(LLA-co-CL) none none 85:15 poly(LLA-co-CL) none none 70:30poly(LLA-co-CL) none none poly(L-lactide) none none DCM 3 polydioxanonenone none DCM 95:5 poly(LLA-co-CL) + none none DCM 4-5 85:15poly(LLA-co-CL) (1:1 w/w) 95:5 poly(LLA-co-CL) + none none DCM 4-5 70:30poly(LLA-co-CL) (1:1 w/w) 95:5 poly(LLA-co-CL) + none none DCM 4-5poly(ε-caprolactone) (90:10, 95:5 or 99:1 w/w) 85:15 poly(LLA-co-GA) +none none DCM 4-5 85:15 poly(LLA-co-CL) (9:1 or 7:3 w/w) 85:15poly(LLA-co-GA) + none none DCM + 6 polyglycolide (3:7 w/w) HFP 85:15poly(LLA-co-GA) + none none DCM 7 polydioxanone (9:1 w/w) 85:15poly(LLA-co-GA) + none none DCM 7 polypropylene carbonate (9:1 or 8:2w/w) 85:15 poly(LLA-co-GA) + none none DCM 7 polyethylene carbonate (9:1w/w) 85:15 poly(LLA-co-GA) + none none DCM 7 PEG (95:5 or 99:1 w/w)85:15 poly(LLA-co-GA) + none none DCM 7 PVP (90:10, 95:5, 97.5:2.5 or99:1 w/w) 85:15 poly(LLA-co-GA) + none none DCM 7 POECO (99:1, 99.5:0.5or 99.9:0.1 w/w) 85:15 poly(LLA-co-GA) + none none DCM 7polydimethylsiloxane (92.5:7.5, 95:5, 97:3 or 99:1 w/w) 85:15poly(LLA-co-GA) + none none DCM 7 Nylon 12 (9:1 or 8:2 w/w) 85:15poly(LLA-co-GA) carbon none 95:5, 99:1 DCM 10 nanotubes or 99.9:0.190:10 poly(LLA-co-TMC) carbon none 95:5 or 99:1 DCM 10 nanotubespoly(L-lactide) carbon none 95:5, 97:3, DCM 3 nanotubes or 99.5:0.5poly(L-lactide) carbon none 96.5:0.5:3 DCM + 3 nanotubes + or MeOH NaCl98.5:0.5:1 85:15 poly(LLA-co-GA) BHT none 1:1, 100:1 DCM 7 or 500:1poly(L-lactide) BHT none 500:1 DCM 3 poly(L-lactide) L-lactide none93:7, 95:5, DCM 3 99:1 or 99.5:0.5 poly(L-lactide) hydroxy- none 97:3DCM 3 apatite whiskers 85:15 poly(LLA-co-GA) barium none 10:2.5 DCM 10sulfate 85:15 poly(LLA-co-GA) calcium none 90:10, 95:5 DCM + 6-7chloride or 97.5:2.5 MeOH 85:15 poly(LLA-co-GA) sodium none 90:10 orDCM + 6-7 chloride 95:5 MeOH poly(L-lactide) sodium none 90:10, 93:7DCM + 3 chloride or 99:1 MeOH 85:15 poly(LLA-co-GA) DCM none 1 wt % DCMpoly(L-lactide) DCM none 1.5 wt % DCM poly(L-lactide) DMSO none 8:2,9:1, DCM 3 95:5 or 99:1 85:15 poly(LLA-co-GA) none myolimus 22:1, 44:1DCM 7 or 66:1 85:15 poly(LLA-co-GA) none myolimus + 66:1:0.3 DCM 7dexametha- sone acetate poly(L-lactide) none novolimus 93:7, 95:5, DCM 399:1 or 99.5:0.5 CL = ε-caprolactone GA = glycolide LLA = L-lactide TMC= trimethylene carbonate PEG = polyethylene glycol POECO =polyoxyethylated castor oil PVP = polyvinylpyrrolidone BHT = butylatedhydroxytoluene DCM = dichloromethane DMSO = dimethylsulfoxide HFP =1,1,1,3,3,3-hexafluoro-2-propanol MeOH = methanol

TABLE 5 Compositions of coatings on stents P + D P:D Ratio Conc'n in“Dry” (w/w) in Spray Solvent Coating Polymer (P) Drug (D) SolventSolvent (mg/mL) Weight (μg) 85:15 poly(LLA-co-GA) myolimus 3:2 DCM 1.67or 3 125 85:15 poly(LLA-co-GA) novolimus 3:2 DCM 1.67 260 85:15poly(LLA-co-GA) myolimus + 9:2:1.3 DCM 1.67 dexamethasone acetatepoly(L-lactide) myolimus 3:2 DCM 5 125 85:15 poly(LLA-co-GA) none DCM1.67 260 poly(ε-caprolactone) none DCM 1.67 250 90:10 poly(LLA-co-CL)novolimus 3:2 DCM 1.67 235 (first coating) 90:10 poly(LLA-co-CL) noneDCM 1.67 200 (outer coating) poly(L-lactide) none DCM 1.67 220 (firstcoating) poly(L-lactide) novolimus 3:2 DCM 1.67 200 (outer coating) CL =ε-caprolactone GA = glycolide LLA = L-lactide DCM = dichloromethane

Example 2 Fabrication of Stents from Annealed Polymeric Tubes

A solution containing a 1:22 weight ratio of myolimus and an amorphouspoly(L-lactide-co-glycolide) copolymer comprising 85% L-lactide and 15%glycolide in dichloromethane was prepared. A polymeric tube was made byspraying the polymer and drug solution onto a mandrel rotating at 80 rpmand moving longitudinally at a rate of 0.050 inch/min. The resultingtube had a thickness of about 0.21 mm prior to heat and vacuumtreatments. The tube was subjected to reduced pressure, heated underreduced pressure, annealed, and then cooled to ambient temperature. Thethickness of the tube was about 0.18 mm after the heat and vacuumtreatments. A stent having the pattern of FIG. 4 (shown in a crimpedstate) was cut from the annealed tube using a UV laser. The stent wascrimped and mounted onto a balloon-catheter. The resulting stentdelivery system was packaged in a pouch and sterilized by exposure toe-beam radiation (30 kGy total dose).

The radial strength of the stent after laser cutting, after crimping,after e-beam sterilization, or after radial expansion at the T_(g) ofthe poly(L-lactide-co-glycolide) copolymer, with heat treatment(annealing) or without heat treatment of the polymeric tube from whichthe stent was cut, was tested at 37° C. in saline solution. The resultsare shown in Table 6 below. In each test scenario, the stent cut from anannealed tube (“heat-treated stent”) exhibited higher radial strengththan the stent cut from a non-annealed tube (“non-heat-treated stent”).

TABLE 6 Comparison of radial strength of heat- treated andnon-heat-treated stents Not Heat- Heat- State of the Stent TreatedTreated Radial strength after laser cutting stent 7 Psi 14 Psi  Radialstrength after crimping stent 6 Psi 9 Psi Radial strength after e-beamsterilization 3 Psi 8 Psi (30 kGy) Radial strength after radialexpansion at T_(g) n/a 12.5 Psi  

TABLE 7 Physical properties of carbon nanotube-reinforced polymericstents Radial Strength Stiffness % Composition of Stent (psi) (N/mm²)Recoil 1 wt % MWCNTs, 90:10 20.4 1.3 5.1% poly(LLA-co-TMC) 5 wt %MWCNTs, 90:10 19.7 1.4 4.9% poly(LLA-co-TMC) 1 wt % MWCNTs, 85:15 7.81.1 −1.6% poly(LLA-co-GA) 5 wt % MWCNTs, 85:15 15.9 1.8 5.0%poly(LLA-co-GA) 1 wt % MWCNTs, PLLA 20.0 NA 6.5% 2 wt % MWCNTs, PLLA19.5 NA 6.4% 3 wt % MWCNTs, PLLA 17.9 NA 5.5% GA = glycolide LLA =L-lactide TMC = trimethylene carbonate MWCNTs = Multi-Walled CarbonNanotubes NA = not available

Physical properties were also measured on stents having a body composedof poly(L-lactide) homopolymer and 3 wt % Multi-walled Carbon Nanotubes(MWCNTs) and a coating containing 3:2 (w/w) of 85:15poly(L-lactide-co-glycolide) and myolimus. The MWCNTs had substantiallysimilar physical dimensions as the MWCNTs described in this Example. Thestents were made according to procedures substantially similar to thosedescribed in this Example and had the pattern of FIG. 1. Radialstrength, stiffness and % recoil of the stents were measured after theywere heated at 70° C., crimped, mounted on a balloon, and sterilizedwith e-beam. The stents exhibited a mean radial strength of 22.8 psi,mean stiffness of 1.3 N/mm², and a mean % recoil of 4.8%.

Example 3 Analysis of Residual/Internal Stress of Stents Cut fromPolymeric Tubes Made by Spraying

Stents having the pattern of FIG. 1 were laser cut from polymeric tubesmade by spraying. To analyze residual/internal stress in the uncoated,as-cut stents, the stents were exposed in ambient environment to atemperature at about the T_(g) or about 20° C. above the T_(g) of thepolymeric material composing the body of the stent. The amount ofshrinkage of the stents as measured by % change in length and % changein outer diameter (OD) was measured over a period of 1 hour or 24 hours(Table 8). Without using any prior stabilization treatment (e.g.,heating and pre-shrinkage), the stents exhibited reduction in lengthand/or OD of no more than 5%, which suggests that the stents cut frompolymeric tubes made by spraying had minimal residual/internal stress.

TABLE 8 Reduction in length and outer diameter (OD) of heated stents 1hr 24 hr 1 hr 24 hr % % % % Temp. Change in Change in Change ChangeComposition of Stent (° C.) Condition Length Length in OD in OD 90:10poly(LLA-co-CL) 50 at Tg 2% 3% 2% 2% 90:10 poly(LLA-co-CL) 50 at Tg 3%3% 2% 3% 90:10 poly(LLA-co-CL) 50 at Tg 2% 3% 1% 2% 90:10poly(LLA-co-CL) 70 20° C. above Tg 4% 4% 2% 3% 90:10 poly(LLA-co-CL) 7020° C. above Tg 4% 4% 3% 3% 90:10 poly(LLA-co-CL) 70 20° C. above Tg 3%3% 3% 3% 95:5 (w/w) PLLA + PCL 50 at Tg 0% 0% 1% 2% 95:5 (w/w) PLLA +PCL 50 at Tg 0% 0% 1% 1% 95:5 (w/w) PLLA + PCL 50 at Tg 0% 0% 1% 1% 95:5(w/w) PLLA + PCL 70 20° C. above Tg 1% 0% 3% 3% 95:5 (w/w) PLLA + PCL 7020° C. above Tg 1% 2% 4% 4% 95:5 (w/w) PLLA + PCL 70 20° C. above Tg 0%1% 4% 5% 95:5 poly(LLA-co-CL) 50 at Tg 1% 1% 1% 1% 95:5 poly(LLA-co-CL)50 at Tg 1% 1% 1% 1% 95:5 poly(LLA-co-CL) 50 at Tg 1% 2% 0% 2% 95:5poly(LLA-co-CL) 70 20° C. above Tg 4% 5% 3% 3% 95:5 poly(LLA-co-CL) 7020° C. above Tg 4% 5% 3% 3% 95:5 poly(LLA-co-CL) 70 20° C. above Tg 4%4% 3% 3% PCL = poly(ε-caprolactone) PLLA = poly(L-lactide)poly(LLA-co-CL) = poly(L-lactide-co-ε-caprolactone) (molar ratio ofmonomers indicated)

Example 4 Myolimus Eluting Bioresorbable Coronary Stent System in thePorcine Model

Studies were performed in a porcine model with the Myolimus ElutingBioresorbable Coronary Stent System which combines a polymer stentcoated with a thin topcoat layer of polymer with Myolimus. The stents inthe studies comprised PLLA, PLLAPGA, PLLAPCL, Poly (Llactide-co-Glycolide) and poly(L lactide-co-caprolactone). At least oneof the studies is described below. The nominal drug dose in the coatingon the 14 mm length stent is 40 μg of Myolimus and coating ispoly(L-lactide-co-glycolide).

The purpose of the studies are to evaluate the efficacy and safety ofthe polymeric degradable drug eluting stent after a period of 28±2 daysand open ended timepoint (OE). The vascular response, including thearterial minimal lumen diameter and percent stenosis, will be evaluatedin all vessels using quantitative vessel angiography (QCA) at 28±2 daysand at an OE endpoint with a follow up procedure at 90±3 days, 180±5days and 270±14 days. Optical coherence tomography (OCT) will also beperformed at these time points to assess stent apposition and recoil.Additionally, histopathologic analysis of the coronary arteries will beperformed at 28±2 days and the OE timepoint to evaluate the cellularresponse to the stents. Another purpose of this study is to evaluatepharmacokinetics (PK) of the released drug at 3 days, 7 days, 28±2 days,and longer timepoints; drug release will be assessed by analysis of thedrug remaining on the stents and uptake of the drug by the tissue. Inaddition, the polymer degradation is also evaluated by evaluating themolecular weight of the polymer remaining on the stent. The product sizeof 3.0×14 mm is used in the study.

A nonatherosclerotic swine model was chosen. Hybrid farm pigs(Landrance-Yorkshire) were selected for use in studies up to 90 days inlength and Yucatan Mini Swine were selected for use in the 180 day andlonger term studies due to starting size and growth expectations. Whenpossible, stents are implanted in the 3 coronary arteries (leftcircumflex artery [LCx], left anterior descending artery [LAD] and rightcoronary artery [RCA]), and in the left and right internal mammaryarteries (IMAs) per animal.

Upon assignment to the study and until sacrifice, animals will bemonitored and observed at least twice a day. To prevent or reduce theoccurrence of thrombotic events, animals are treated daily, withacetylsalicylic acid (325 mg, per os [PO]) and clopidogrel (300 mg onthe first day and 75 mg daily afterwards, PO), beginning at least 3 daysbefore intervention and continuing until sacrifice. The drugs will becrushed to powder and mixed with their food; therefore, treatment willnot be administered when animals are fasted. Fasting (food, includingany dietary supplements) will be conducted the morning prior tointerventional procedures and scheduled sacrifice. Water will not bewithheld. Animals will be tranquilized with ketamine, azaperone andatropine administered intramuscularly [IM]. Animal weight will berecorded. Anesthesia induction will be achieved with propofol injectedintravenously [IV]. Upon induction of light anesthesia, the subjectanimal will be intubated and supported with mechanical ventilation.Isoflurane in oxygen will be administered to maintain a surgical planeof anesthesia. Intravenous fluid therapy will be initiated andmaintained throughout the procedure. The rate may be increased toreplace blood loss or to correct low systemic blood pressure. To preventpostoperative infection, animals will be given prophylactic antibioticDraxxin® IM. Additional doses may be administered as deemed appropriate.In order to prevent pain sensitization and minimize postoperative pain,Torbugesic (butorphanol) will be administered IM as preemptiveanalgesia. After induction of anesthesia, the left or right femoralartery will be accessed through an incision made in the inguinal region.Bupivacain IM will be infiltrated into the femoral access site toachieve local anesthesia and manage pain after surgery. An arterialsheath will be introduced and advanced into the artery. An initialheparin bolus will be administered and ACT will be measured at leastevery 30 minutes and recorded. The device will not be introduced untilACT is confirmed to be >300 seconds. If ACT is <300 seconds, additionalheparin will be administered. Under fluoroscopic guidance, a guidingcatheter will be inserted through the sheath (6F) and advanced to theappropriate location. After placement of the guiding catheter,nitroglycerin will be delivered to achieve vasodilatation andangiographic images of the vessel will be obtained with contrast mediato identify the proper location for the deployment site (designatedpre-stent angiographies). A segment of coronary artery will be chosenand a guidewire will be inserted into the chosen artery. QCA will beperformed at this time to document the reference diameter for stentplacement. OCT will be performed before implantation to confirm vesselsizing at three locations per coronary vessel.

Stent Deployment Procedures: The stent will be introduced into theselected artery (diameter range of 2.6 to 3.0 mm if possible) byadvancing the delivery system through the guiding catheter, over theguide wire to the deployment site. After the stent enters the guidecatheter, there will be at least a one minute soak wait before deployingthe stent. The stent will then be deployed. The balloon will be inflatedat a slow rate: starting with 10 second intervals per atmosphere, bringthe balloon to 2 atm. Further expansion completed at 3-5 secondintervals for each subsequent atmosphere of pressure. This is approx.40-50 seconds to nominal pressure. Final pressure is maintained for20-30 seconds. An angiogram of the balloon at full inflation will berecorded (designated balloon angiography) and the inflation pressurewill be noted. After the target stent to artery ratio has been achieved,vacuum will be slowly applied to the inflation device to deflate theballoon. Complete balloon deflation will be verified fluoroscopically. Asecond inflation may be conducted if a stent is not well apposed againstarterial wall or if an animal is at risk. Injection of nitroglycerinwill be repeated and a final angiogram of the treated vessel will beperformed (designated post-stent angiography) to document devicepatency, and TIMI flow Implantation will be repeated in the othervessels.

OCT will be performed on all animals to assess stent recoil. OCT will beperformed before implantation to confirm vessel sizing at threelocations per coronary vessel. After all implants are completed, OCTwill be performed again for the same (first) stent, followed by everyother stent implanted in the coronaries (designated end of implant OCT).

Following the successful deployment of stents and completion ofangiography, all catheters and the sheath will be removed from theanimal and the femoral artery will be ligated. The incision will beclosed in layers with appropriate suture materials. An antibioticointment will be applied to the wound.

The fluoroscopic output from the stent implantation (pre-stent, ballooninflation, post-stent, and end of implant) and at explantation (final)was recorded in digital format. From these images, QCA measurements wereobtained for the 28 day and 180 day cohort animals. QCA was alsoperformed at the 90 day follow-up for the 180 day cohort animals. OCTimaging was performed in each animal after the first stent was implantedand after all implants had been completed. OCT was also performed priorto sacrifice on the 28 day Cohort of animals. OCT was performed at a 90day follow-up on the 180 day cohort. Analysis of each vessel mayinclude: qualitative evaluation for evidence of lumen narrowing(in-stent and marginal), migration, presence of dissection, presence ofaneurysms, presences of thrombosis and TIMI flow. Elastin stainedsections were examined using light microscopy, image capture, andquantitative morphometric computer-assisted methods. Severalsemi-quantitative parameters were employed to assess the biologicalresponse of vascular tissue to the stents by light microscopyexamination of stained sections. Other organ samples were observed forany abnormal findings. Scores to describe vessel injury, inflammation,fibrin deposition, calcification and endothelialization were performed.

Pharmacokinetics Analysis: The drug remaining on the stents was measuredusing an HPLC-UV analytical method for measuring the drug total contenton stents. The drug tissue concentration in the explanted surroundingtissue (artery wall) as well as neointima containing some remainingstent struts (at later timepoints) were measured using a LC/MSbioanalytical method.

Analytical method for determination of polymer Stent Mass and MolecularWeight: Polymer Stent Mass and molecular weight (MW) determination wereconducted using Gel Permeation Chromatography (GPC).

Results: FIG. 6 shows a typical series of OCT images from the implant.FIG. 7 shows the stent and lumen diameter at various time points. Theacute and end of implant stent diameter were similar, indicating minimalrecoil. The mean lumen diameter was at least maintained or increasedover time. FIG. 8 depicts the method used to calculate % stenosis andFIG. 9 shows the observed % stenosis and it can be seen that the %stenosis was maintained to 270 d. Table 9 shows the histopathologyresults and FIG. 10 shows the vascular response up to 270 days. FIG. 11shows the Pharmacokinetic results from the study. FIG. 12 shows thedegradation of the implant—the trendline supports approximately 1-2 yrdegradation by Mw. FIG. 12A shows in vivo sample degradation rate ofbiodegradable polymer stent material through 180 days and calculateddegradation rate by MW and FIG. 12B shows in vivo sample degradationrate of biodegradable polymer stent material through 270 days andcalculated degradation rate by MW. FIG. 12C shows polymer mass decreaseover time.

TABLE 9 Histopathology results Pathology Score 28 day 90 day 180 day 270day Injury Score 0.42 ± 0.22 1.31 ± 1.01 0.69 ± 0.54 0.67 ± 0.19Inflammation 0.68 ± 0.26  1.5 ± 1.31 0.82 ± 1.13 0.25 ± 0.17 ScoreFibrin Score 1.79 ± 0.32 0.32 ± 0.19 0.13 ± 0.04 0.09 ± 0.05 Endotheli-2.03 ± 0.81 1.67 ± 0.37 1.78 ± 0.69 1.67 ± 0.34 alzation Score

Below in Table 10 is an example of in vivo QCA measurement of recoilafter expansion of the stent using two measurements techniques the firstbased on mean stent diameter and the other based on mean minimumdiameter of the stent.

TABLE 10 Example of in vivo QCA measurement of recoil after expansion ofthe stent Animal study of Biodegradable polymer stent of presentinvention Coronary arteries End of Recoil Pre-Stent Balloon implantBased on Recoil Animal Mean Mean Mean Min Mean Based on Number ArteryLocation (mm) (mm) (mm) (mm) diam Min diam D28-01 LAD mid 2.60 2.50 2.462.20 1.6% 12.0% D28-01 RCA dist 2.76 3.02 2.75 2.43 8.9% 19.5% D28-02LAD mid 2.75 2.88 2.59 2.38 10.1% 17.4% D28-02 RCA mid 2.72 2.62 2.592.28 1.1% 13.0% D180-01 LAD mid 2.44 2.66 2.70 2.51 −1.5% 5.6% D180-01RCA mid 2.66 2.58 2.78 2.59 −7.8% −0.4% D180-02 LAD mid 2.76 2.93 2.982.72 −1.7% 7.2% D180-03 LAD mid 2.52 2.57 2.65 2.45 −3.1% 4.7% D180-03LCx mid 2.61 2.65 2.64 2.30 0.4% 13.2% D180-03 RCA dist 2.57 2.91 2.732.50 6.2% 14.1% D180-04 LAD mid 2.57 2.57 2.80 2.64 −8.9% −2.7% D180-04LCx dist 2.85 3.18 3.06 2.70 3.8% 15.1% D180-04 RCA dist 2.71 2.50 2.972.72 −18.8% −8.8% Ave −0.7% 8.4% Max 10.1% 19.5% Min −18.8% −8.8% SD7.8% 8.5% n 13 13

Below in Tables 11, 12 and 13 are examples of different animal studiesof biodegradable polymer of present invention with implantationprocedures similar to Example 4 with follow-up at 28 days, 90 days, 180days, and 270 days.

TABLE 11 Results of animal study of biodegradable polymer (90 days, 180days, 270 days). At 90 days At 180 days At 270 days OCT measurement MeanSD n Mean SD n Mean SD n Scaffold 2.8 0.5 13 2.6 0.5 7 3.0 0.9 5Diameter (mm) Lumen 2.2 0.4 13 2.2 0.4 9 2.4 0.6 5 Diameter (mm)Scaffold 6.6 1.8 10 6.8 2.3 7 7.4 3.8 4 Area (mm²) In-Scaffold 2.4 0.910 2.9 1.6 7 3.2 2.1 4 Intimal Area (mm²) Lumen Area 3.8 1.4 10 4.0 1.69 4.6 2.4 5 (mm²) % stenosis 37% 9% 10 41% 10% 7 41% 5% 4 (Intimal Area/Scaffold Area)

TABLE 12 Results of animal study of biodegradable polymer (28 days, 90days, 180 days). At 28 days At 90 days At 180 days OCT measurement MeanSD n Mean SD n Mean SD n Scaffold Diameter 2.6 0.1 3 3.0 0.4 8 4.1 1.3 8(mm) Lumen Diameter 2.1 0.2 3 2.2 0.2 8 2.4 0.2 8 (mm) Scaffold Area 6.40.7 3 8.4 1.9 8 8.9 1.8 8 (mm²) In-Scaffold Intimal 2.5 0.2 3 4.1 1.7 84.1 1.3 8 Area (mm²) Lumen Area (mm²) 3.4 0.5 3 3.8 0.7 8 4.5 0.8 8 %stenosis (Intimal 40% 3% 3 47% 10% 8 45% 6% 8 Area/Scaffold Area)

TABLE 13 Results of animal study of biodegradable polymer (28 days, 90days, 180 days). OCT At 28 days At 90 days At 180 days measurement MeanSD n Mean SD n Mean SD n Scaffold 2.7 0.1 7 2.8 0.2 7 3.0 0.3 7 Diameter(mm) Lumen 2.2 0.3 7 1.9 0.3 7 2.2 0.3 7 Diameter (mm) Scaffold Area 6.90.7 7 7.5 1.3 5 8.5 1.5 7 (mm²) In-Scaffold 2.5 4.0 7 4.0 1.9 5 4.4 1.57 Intimal Area (mm²) Lumen Area 4.0 1.2 7 2.8 1.0 7 3.7 1.0 7 (mm²) %stenosis 36% 11% 7 52% 19% 5 52% 13% 7 (Intimal Area/ Scaffold Area)

Example 5 Processing of Stents and Tubes

This example illustrates processing of stents and tubes utilizing someembodiments. Various other embodiments may be incorporated in theseexamples or other examples and are within the scope of the disclosedpresent invention.

A. Processing of a Polymeric Stent Example 5A

A stent is patterned from a tube formed using extrusion (or optionallyusing spraying, dip coating, molding, or 3D printing) from polylactidematerial, more preferably, Poly(L-lactide) (or optionally from aco-polymers such as Polylactide-co-polyglycolide orpolylactide-co-polycaprolactone; or blends of polylactides,polyglycolides, and polycaprolactones; or combination thereof; invarious polymer or co-polymer ratios such as 80:20 to 99:01). Thetubular body has an initial inner diameter of about 0.5 mm (0.020″) butoptionally can have an initial diameter ranging from about 0.25 mm(0.01″) to 2 mm (0.079″). The tube is treated by at least one of heat,pressure, and drawing at temperature above Tg of the material and belowTm for duration ranging from a fraction of a second to one hour toexpand the tube to a second uniform inner diameter of about 3 mm(0.118″) which is about the diameter of the intended deployment diameterof a the stent when the stent is deployed to about 3 mm or to at leastthe intended deployment diameter when the stent is deployed to about 3mm or above in this example (intended deployment diameter can also bethe nominal labeled diameter of the stent or deploying balloon or theactual deployed diameter of the stent). Optionally, the second innerdiameter of the tube or the stent can range from 0.9-1.5 times anintended deployment diameter of the stent. The tube or the stent isoptionally treated by heating at about Tg or above Tg (for example 90°C.), ranging from a fraction of second to 24 hours when the tube is atthe second inner diameter. Optionally a mandrel is inserted inside thetube while the heat treatment is applied and also optionally the tube isheld into position over the mandrel to control shrinkage of the tube.The tube is cooled after heat treatment or optionally quenched quicklyto a temperature below Tg or below the crystallization temperature or toambient temperature or below ambient temperature. The tube is patternedinto a stent at about the second inner diameter or optionally below thesecond inner diameter. The patterned stent is coated with the drugNovolimus (e.g. 5 micrograms/mm) or optionally with a mixture ofNovolimus and a polymer or co-polymer such as a PLLA polymer or PLLA-PGAco-polymer. The coated stent is optionally placed in a vacuum for atotal of 36 hours and then crimped to a diameter smaller than theintended deployment diameter using a gradual heat (at about Tg or belowTg) and pressure or mechanical force from about 10 seconds to about 30minutes. The stent is crimped onto the delivery system or optionallycrimped and then mounted or fitted onto a delivery system such as aballoon catheter. After crimping, the stent delivery system is packagedin a sterile barrier (i.e., in a foil pouch) and can be sterilized byebeam or ethylene oxide cycle. The mounted stent and delivery system inthe example are sterilized using E-beam sterilization. The sterilizedstent is subjected optionally to one additional treatment by heating thepackaged stent to a temperature below Tg (example 30° C.) for a durationranging from 1 minute to 7 days). The stent material Tg after treatmentis above 35° C. and below 55° C. The crystallinity of the stent materialafter treatment ranges from about 0% to 60%. (Optionally thecrystallinity after treatment can range from 0% to 30% or 0% to 40% or0% to 55%). The stent is capable of radial expansion at body temperatureand have sufficient radial strength to support a body lumen, oroptionally 3 psi or greater. The stent optionally has recoil from anexpanded condition of less than 10%.

Other embodiments are:

Example 5A.1

A stent prosthesis as in example A wherein the heat treatment of thetubular body or stent at about Tg or above Tg for a duration rangingfrom a fraction of a second to about 24 hours takes place when the tubediameter is 0.9-1.5 times the intended deployment diameter.

Example 5A.2

A stent prosthesis as in example A wherein the heat treatment of thetubular body or stent at about Tg or above Tg for duration ranging froma fraction of a second to about 24 hours takes place when the tubediameter is 0.9-1.5 times the intended deployment diameter andoptionally a treatment by heat of the tubular body below Tg takes placewhen the tube diameter is below 0.9 times the intended deploymentdiameter.

Example 5A.3

A stent prosthesis as in example A wherein the heat treatment of thetubular body or stent when the tube diameter is 0.9-1.5 times theintended deployment diameter is always about Tg or below Tg for aduration ranging from a fraction of a second to about 24 hours.

Example 5A.4

A stent prosthesis as in example A wherein the second inner diameter ofthe tube or the stent is 0.95-1.5 times an intended deployment diameter,or 1-1.5 times an intended deployment diameter, or 1.05-1.5 times anintended deployment diameter, or 1.1-1.5 times an intended deploymentdiameter.

Example 5A.5

A stent prosthesis as in example A wherein the treatment by heat atabout Tg or above Tg for the tube or stent when the diameter is 0.9-1.5times an intended deployment diameter is for a short duration rangingfrom a fraction of a second to less than one hour, preferably from afraction of a second to less than 30 minutes, and more preferably from afraction of a second to less than 15 minutes.

Example 6 Securing the Stent on Delivery System

As a means to retain the stent on the balloon of a delivery catheter, ablockade-like bump on the proximal end, distal end or both ends of thestent can be formed on the balloon or part of the balloon (FIG. 2). Thebump can be deflated partially or fully by means of a vacuum on thecatheter lumen as part of the deflation port of the balloon or aseparate/independent deflation port. The bumps deflate or shrink orbecome smaller upon inflation of the balloon or upon deflation of theballoon or upon pulling vacuum on the balloon or upon pulling vacuum onthe separate bump port. The bump prevents or minimizes the movement ofthe stent during introduction and delivery of the stent to the lesion.

Another means for retaining the stent is by the presence of a cap on theproximal end, distal end, or both ends of the stent. Each cap covers aportion of the stent, preferably from approximately 0.1 to 2 millimeterof the stent. The cap can be made from a solid tube, spongy tube, weaveor braided tube, or laser cut tube with patterning, or a portion of theballoon material itself and affixed to one end of the catheter. The capcan fit snuggly or tightly around the stent. The inner diameter of thecap can be slightly larger than the crimped diameter of the stent,preferably same as the crimped diameter, and more preferably, smallerthan the diameter of the crimp diameter. The remaining cap may cover theballoon material adjacent to the stent and may extend further to coverouter member (proximal cap) or the tip (distal cap) of the deliverycatheter. The cap can have uniform diameter (inner diameter samethroughout the length of the cap), it can have a larger inner diameteron the side where it covers the stent and smaller inner diameter on theside where it covers the outer member/tip of the delivery catheter. Oneor more exposed edges of the cap can be beveled. Preferably the cap isglued to the delivery catheter (affixed) when it is not in contact withthe stent or balloon so as to prevent it from flowing away. Uponexpansion of the balloon and ensuing expansion of the stent, the capretracts or releases from the stent and at a certain balloon diameter,no longer covers the stent and allows the stent to expand freely.

Another means for retaining the stent is the use of an adhesive such aswaterproof permanent adhesive, non permanent adhesive, or solvent suchas tetrahydrofuran, dichloromethane, chloroform, or the like. Theadhesive is applied on the balloon or catheter such that there is one ormore tongue or groove formed within the adhesive mass. The tongue orgroove can be the same or smaller than a stent feature such as a link,strut, marker tab or hole, crown, tab, flap or other which serves as thegroove or tongue (reverse of the adhesive shape). The shape of thetongue or groove is dependent on the stent feature. The depth of thetongue or groove can be greater than the stent thickness, same as thestent thickness, or less than the stent thickness. The adhesive can bepositioned at either or both end of the intended stent or elsewherewithin the confines of the stent. A crimped stent is then placed ontothe adhesive and the feature of the stent is snapped into the tongue orgroove of the adhesive mass as a means to retain the stent. When theballoon is expanded, the stent feature snaps out of the groove.

Another means for retaining the stent is the use of heat to heat sealthe stent onto the balloon surface. A stent inside a sheath is insertedover the balloon. The stent is heated to about or below the Tg of thecoating of the stent or the stent and then the balloon is pressurizedcausing the stent to be heat sealed to the balloon. In another means,the stent with or without a sheath on a balloon can be placed inside aheated crimper set at about or below the Tg of the coating on the stentor the stent and the crimper is allowed to closed. The balloon ispressured causing the stent to be heat sealed to the balloon. Stentcoating can be such that the coating itself or an added top layer ofcoating is made from a material that has a lower Tg than the stentitself. Examples of such a layer can be made of 70:30 PLLA-co-CL or85:15 PLLA-co-CL or higher ratios of CL, or PGA, PLLA-GA with higherratio of GA, PDLLA, polymers with Tg at or below 55 degrees Celsius, orthe like or combination thereof.

Another means for retaining the stent is the use of an adhesive such aswaterproof permanent adhesive or non permanent adhesive to affix ananchoring device. The anchoring device has a grooves or tongue that canbe the same or smaller that a stent feature such as a link, strut,marker tab or hole, crown, tab, flap, or other groove or tongue (reverseof the anchor device). The shape of the tongue or groove is dependent onthe stent feature. The depth of the tongue or groove can be greater thanthe stent thickness, same as the stent thickness, or less than the stentthickness. One or more anchoring device is snapped onto the stentfeature or features. The stent can be crimped before or after attachmentto the anchoring device. The stent is mounted over the balloon and theanchoring device is attached mechanically to the balloon or by use ofadhesives or welding means. The anchoring device can have an elasticband which goes around the balloon as a means to be attachedmechanically to the balloon. This band stretches as the balloon isexpanded. As the stent and the band expand, the grip of the tongue orgroove will release the stent.

Another example of securing the stent is to apply or modify the surfaceof the catheter or balloon catheter is such a way to retain or hinderthe stent from longitudinal movement upon delivery of the stent into abody lumen and allows the stent to expand or deploy in the body lumen atbody temperature.

Another example of securing the stent is to apply an adhesive to atleast one side of the stent (abluminal or luminal) which when crimpingthe stent onto the catheter or the balloon catheter creates a bondsufficient to minimize or prevent the stent from moving in thelongitudinal direction or expanding in the radial direction prior toactive deployment by the operator.

Another means to secure the stent on delivery system is to incorporate asheath over the stent that is retracted to deploy the stent to anintended deployment diameter or to a partial deployment diameter belowan intended deployment diameter.

Example 7 Methods to Control Tg to a Desired Tg Between 35° C. to 50° C.or Above 37° C. to 45° C.

To control Tg of stent material to allow expansion at body temperatureor other desired temperatures. For example, a desired Tg between 35° C.and 50° C. to allow the stent to expand at body temperature can beachieved through one or more sequence of treatments to control the Tgstarting from forming the tube to the final product where the desired Tgis achieved. A polymer or co-polymer tube such as PLLA-PCL or PLLA-PGAwhere the tube is formed using extrusion, spraying, dip coating,molding, or 3D printing and having a Tg after forming about 55° C. Thetube is treated by at least one of heating, solvent removal orintroduction, additive removal or introduction, pressurizing,stretching, vacuum, sterilization, and patterning, in a certainconfiguration or sequence to achieve a desired Tg for the stent materialafter treatment to be between 35° C. and 50° C. (optionally greater than37° C. and below 45° C.) such that the stent is capable of radialexpansion in a body lumen and have sufficient radial strength to supporta body lumen.

Another example is a stent with a transitional temperature, Tg, between37° C. to 55° C.—one method to control the stent Tg is by using acopolymer, terpolymer, or the like for making the stent. For example, acopolymer made from 70:30 to 95:05 of L-lactide and epsilon-caprolactonemolar ratios, can result in a stent having a range of Tg from 37° C. to55° C., respectively. Another method is to fabricate tube using aheatless process such as dipping or spraying to form a tube. Forexample, a tube, which can be patterned into a stent, can be fabricatedby dipping a mandrel onto a concentrated solution of material having aTg less than 55° C. For example, a tube can be made by spraying asolution onto a mandrel. After dipping or spraying, the solvent isallowed to evaporate by vacuuming and or exposure to carbon dioxide athigh pressures (such as 700 psi for 24 hours). The use of this heatlessspraying or dipping process minimizes the formation of crystallinestructures within the polymer, thereby resulting in the minimum possibleTg. Another method is to add one or more molecules into the polymer usedto fabricate the stent. Molecules can be a solvent such as methylenechloride, DMSO, or others, plasticizers such as lactide, caprolactone,lactic acid, L-lactic acid, D-lactic acid, DL-lactic acid, p-dioxanone,epsilon-caprolic acid, alkylene oxalate, cycloalkylene oxalate, alkylenesuccinate, β-hydroxybutyrate, substituted or unsubstituted trimethylenecarbonate, 1,5-dioxopan-2-one, 1,4-dioxepan-2-one, glycolide, glycolicacid, L-lactide, D-lactide, DL-lactide, meso-lactide, combinationthereof, or others, low Tg polymers such as polyvinylpyrrolidone,polyethylene glycol, polyethylene oxide, castor oil, combinationthereof, or others.

A further method of controlling the Tg of the polymer is by processingsuch as heating, laser cutting, crimping, irradiation, or the like.Exposing the stent or tube used to pattern the stent to these processescan decrease or increase the Tg of the material.

Examples of processing a tube or a stent at a diameter ranging from0.9-1.5 times intended deployment diameter where the stent is expandedat temperature above 37° C. in a body lumen are shown below.

A stent is patterned from a tube made from Poly(L-lactide-co-glycolide)material, preferably having a lactide to glycolide comonomer ratio of83:17 to 88:12. The tube can be formed by spraying. Before it ispatterned into a stent, the tube has an inner diameter that is 90 to150% of the intended stent deployment diameter. As a further example,for a 3 mm stent intended deployment diameter, the tube inner diametercan range from 2.7 millimeter (0.106″) to 4.5 millimeter (0.177″).Another example is for a 3.5 mm intended deployment diameter stent. Thetube inner diameter can range from 3.15 millimeter (0.124″) to 5.25millimeter (0.207″). The tube is heat treated optionally below Tg suchas at 10° C. below the Tg for 30 minutes. Alternatively or optionally,the tube is heated above Tg ranging from a fraction of a second to 5hours (for example at 90° C. for 1 hour). The Tg of the tube after heattreatment is between 30° C. to 55° C. (optionally between 35° C. to 55°C.). The tube is then patterned into a stent, coated with a drug matrixsuch as Poly(L-lactide) based copolymer and Novolimus. The coated stentis vacuumed for 36 hours at approximately 1 torr. The stent is thencrimped at 45° C. (optionally between 30° C. and 45° C., or optionallylower than Tg) onto the balloon of a delivery catheter. The stentdelivery system is packaged in a sterile barrier and sterilized byebeam. After sterilization, the stent delivery system is optionallystabilized at 29° C. for 48 hours. Prior to or during stent deployment,the stent is heated to a temperature greater than 37° C. but below 50°C. (optionally above 37° C. and below 45° C.) to expand the stent to itsintended deployment diameter. (Optionally by a heated catheter orballoon, RF balloon, heated contract agent injected into the artery,heated coil on the catheter shaft proximal to the balloon, or by othermeans). This provides sufficient radial strength to support a body lumenand/or have a recoil from an expanded state of less than 10%.

Another example is a stent patterned from a tube made fromPoly(L-lactide-co-glycolide) material, preferably having a lactide toglycolide comonomer ratio of 80:20 to 95:05. The tube can be formed byspraying. Before it is patterned into a stent, the tube has an innerdiameter that is 90 to 150% of the intended stent deployment diameter.As a further example, for a 3 mm stent, the tube inner diameter canrange from 2.7 millimeter (0.106″) to 4.5 millimeter (0.177″). Anotherexample is a 3.5 mm stent. The tube inner diameter can range from 3.15millimeter (0.124″) to 5.25 millimeter (0.207″). The tube is heattreated below Tg for example at 10° C. below the Tg for 30 minutes. TheTg of the tube after treatment is between 35° C. to 55° C. The tube isthen patterned into a stent, coated with a drug matrix such asPoly(L-lactide) based copolymer and Novolimus. The coated stent isvacuumed for 36 hours at approximately 1 torr. The stent is then crimpedat 45° C. onto the balloon of a delivery catheter. The stent deliverysystem is packaged in a sterile barrier and sterilized by ebeam. Aftersterilization, the stent delivery system is optionally stabilized at 29°C. for 48 hours. The final stent material after treatment issubstantially amorphous. Before or during stent deployment, the stent isheated to a temperature greater than 37° C. and below 50° C. (optionallyabove 37° C. and below 45° C.) to expand it to its intended deploymentdiameter by means such as a heated balloon, RF balloon, heated contractagent injected into the artery, heated coil on the catheter shaftproximal to the balloon, or by other means. The expanded stent hassufficient strength to support a body lumen and/or recoil from anexpanded state of less than 10%.

Another example is a stent is patterned from a tube made fromPoly(L-lactide-co-caprolactone) material, preferably having a lactide tocaprolactone ratio of 80:20 to 99:01. The tube can be formed byspraying. Before it is crimped, the tube has an inner diameter that is90 to 150% of the intended stent deployment diameter. As a furtherexample, for a 3 mm stent, the tube inner diameter can range from 2.7millimeter (0.106″) to 4.5 millimeter (0.177″). Another example is a 3.5mm stent. The tube inner diameter can range from 3.15 millimeter(0.124″) to 5.25 millimeter (0.207″). The tube is heat treated above Tgfor example at 120° C. for 2 hours (optionally fraction of a second to 5hours). The Tg of the tube after treatment is between 35° C. to 55° C.The tube is patterned into a stent, coated with a drug matrix such asPoly(L-lactide) based copolymer and Novolimus. The coated stent isvacuumed for 36 hours at approximately 1 torr. The stent is then crimpedat 35° C. onto the balloon of a delivery catheter. The stent deliverysystem is packaged in a sterile barrier and sterilized by ebeam. Thefinal stent material after treatment has a crystallinity of 25%(optionally between 10% and 50%). Before or during stent deployment, thestent is heated to a temperature greater than 37° C. and below 50° C.(optionally above 37° C. and below 45° C.) to expand it to its intendeddeployment diameter by means such as a heated balloon, RF balloon,heated contract agent injected into the artery, heated coil on thecatheter shaft proximal to the balloon, or by other means. The expandedstent has sufficient strength to support a body lumen and/or recoil froman expanded state of less than 10%.

Example 8 Methods of Fabricating a Stent or a Tube with RadiopaqueMaterial

One method to fabricate a stent with radiopacity is to have cup or holefeatures in the stent design. These cup or hole features are for holdingradiopaque markers that can be higher in thickness, same thickness, orlower thickness as the stent. One or more cup or hole features can be onthe stent. For example, 2 cups can be located at each end of the stentand can be 90 degrees apart. Markers can be made from metals such asgold, tungsten, tantalum, platinum, iridium, alloys of these metals,combination thereof, or other. Markers can also be made from stentmaterial filled with radiopaque agents such asnanoparticles/microparticles/fibers/others made from metal like gold,tungsten, tantalum, platinum, iridium, alloys of these metals,combination thereof, or others; barium compounds like barium sulfate; orcontrast media. The loading of these agents can be from 1 to 80% byweight.

Another method to fabricate a stent with radiopacity is to addradiopaque agent fillers during the spraying, dipping, molding, 3Dprinting, extrusion, or the like. The radiopaque fillers can benanoparticles/microparticles/fibers/others made from metal like gold,tungsten, tantalum, platinum, iridium, alloys of these metals,combination thereof, or others; barium compounds like barium sulfate at1 to 80% by weight filling; or contrast media such as iodinated contrastagents like diatrizoate, metrizoate, ioxaglate, iopamidol, iohexol,ixolian, iopromide iodixanol; Ipodate sodium; sodium iopodate;gadolinium; potassium iodide; or other. The loading of these contrastagents can be from 10 to 80% by weight.

Yet another method is to add molecules that contain iodine, barium,platinum, or heavy metal to the material used to fabricate the stent.These molecules can covalently attached to the material by grafting ontothe polymer chains or crosslinking more than one polymer chains. Thesemolecules contain one or more iodine, barium, platinum, or heavy metals.The percent of these molecules can vary from 1 to 50% by weight.

Yet another method for making the stent radiopaque is to crimp the stentonto the balloon of an infusion catheter. As the stent is beingexpanded, contrast agents are infused into the artery at high pressure,making the artery radiopaque at the site of deployment. Depending on thehydrophobicity and lipophilicity of the contrast agents, these agentswill wash out and the artery will no longer be radiopaque.

Yet another method for making the stent radiopaque is to have a thinradiopaque metal or alloy structure within the stent. This thinradiopaque structure can be made from made from metal like gold,tungsten, tantalum, platinum, iridium, alloys of these metals,combination thereof, or others. The thickness of the structures canrange from 0.0001″ to 0.001″. They can have circular, square,trapezoidal, rectangular, triangular, or other cross-sections. Thestructures can be small corrugated rings, part of or a whole stent,crowns, filaments. A tube of some thickness is first formed by partiallydipping or spraying coating solutions of the stent material onto amandrel. After coating, the thin radiopaque structures are placed incontact, pressed into place, or crimped into place on the partiallydipped or spray tube. The tube with the radiopaque structure is thenfurther dipped or sprayed until the final desired thickness has beenreached. The tube is then patterned into a stent such that theradiopaque structures are partially or fully embedded in the stent.

Yet another method for making the stent radiopaque is to have a thinradiopaque metal or alloy structure within the stent. This thinradiopaque structure can be made from metal like gold, tungsten,tantalum, platinum, iridium, molybdenum, iron, magnesium, alloys ofthese metals, combination thereof, or others. The thickness of thestructures can range from 0.0005″ to 0.001″. They can have circular,square, trapezoidal, rectangular, triangular, or other cross-sections.This structure is then coated with a coating of bioresorbable materialsuch as polylactide, poly(lactide-co-caprolactone),poly(lactide-co-glycolide), or the like.

Example of a stent capable to expand to at least 120% or 1.2 times anintended deployment diameter while keeping an intact stent structureintegrity and optionally having a recoil of less than 15% from anexpanded state (optionally less than 10%, or less than 5%) is shownbelow.

A stent is patterned from a tube made from Poly(L-lactide-co-epsiloncaprolactone) material, preferably having a lactide to epsiloncaprolactone comonomer ratio of 82:10 to 98:02, more preferably at 88:12to 92:08. The tube can be formed using extrusion, molding, dipping, orspraying and treated. The glass transitional temperature, Tg, of thepolymeric material after treatment is greater than 35° C. and less thanapproximately 55° C. The tube is patterned into a stent. Before crimpingthe stent or the tube has an inner diameter that can range from 0.9 to1.5 times its intended deployment diameter. As an example, for a 3 mmintended deployment diameter stent, the inner diameter of the tube orthe patterned stent is between 2.7 millimeter (0.106″) to 4.5 millimeter(0.177″). For a 3.5 mm stent, the inner diameter is between 3.15millimeter (0.124″) to 5.25 millimeter (0.207″). The crimped stent ismounted onto a delivery system, packaged, and sterilized. The stent isexpandable at body temperature to at least 120% of an intendeddeployment diameter (nominal diameter) with sufficient strength tosupport a body lumen and without breakage (fracture) in any of the stentstruts (optionally while maintaining structural integrity of the stent)and optionally with a % recoil of less than 15% from an expanded state.

Example 9 Method to Treat Above Tg at an Expanded Diameter

A tube is formed by spraying or extrusion at diameter x where x is0.8-1.5 times (80 to 150%) an intended deployment diameter, treatment ofthe tubular body to temperature above Tg, patterning at x diameter,crimping, and sterilizing.

A stent is patterned from a tube made from Poly(L-lactide-co-epsiloncaprolactone) material, preferably having a lactide to epsiloncaprolactone comonomer ratio of 82:18 to 98:02, more preferably at 88:12to 92:08. The tube can be formed by extrusion, molding, dipping, orspraying. Before it is patterned into a stent, the tube has an innerdiameter that is 80 to 150% of the intended stent deployment diameter.As a further example, for a 3 mm intended deployment diameter for thestent, the tube inner diameter can range from 2.4 millimeter (0.094″) to4.5 millimeter (0.177″). Another example is an intended deploymentdiameter of at least 3.5 mm stent. The tube inner diameter can rangefrom 2.8 millimeter (0.110″) to 5.25 millimeter (0.207″). The tube isthen heat treated above the Tg of material to increase the crystallinityof the stent by at least 5%. The temperature can range from 60° C. to100° C. for 1 minutes to 24 hours. For example, the tube can be heatedtreated at 90° C. for 2 hours. The tube is patterned into a stent,coated with a drug matrix such as Poly(L-lactide) based copolymer andNovolimus, and crimped at 45° C. onto the balloon of a deliverycatheter. The stent delivery system is the packaged in a sterile barrierand sterilized by ebeam. The stent is radially expandable at bodytemperature having sufficient radial strength to support a body lumen.

Example 10 Tube or Stent with Amorphous Crystallinity after Modification

A polymeric material is sprayed to form tube at x (x is 0.8-1.5 timesintended deployment diameter), treated at about 75° C. for 15 minutes,patterned, crimped, sterilized, post stabilized (optional), wherein thepolymeric material after treatment is amorphous.

A stent is patterned from a tube made from Poly(L-lactide-co-epsiloncaprolactone) material, preferably having a lactide to epsiloncaprolactone comonomer ratio of 88:12 to 92:08. The tube can be formedby spraying. Before it is patterned into a stent, the tube has an innerdiameter that is 80 to 150% of the intended stent deployment diameter.As a further example, for at least a 3 mm intended deployment diameterfor the stent, the tube inner diameter can range from 2.7 millimeter(0.106″) to 4.5 millimeter (0.177″). Another example is a 3.5 mm stent.The tube inner diameter can range from 3.15 millimeter (0.124″) to 5.25millimeter (0.207″). The tube is patterned into a stent, coated with adrug matrix such as Poly(L-lactide) based copolymer and Novolimus. Thecoated stent is vacuumed for 36 hours at approximately 1 torr. The stentis optionally heat treated at 70° C. for 15 minutes. The stent is thencrimped at 30° C. onto the balloon of a delivery catheter over 30minutes (optionally 1 minute to 1 hour). The stent delivery system ispackaged in a sterile barrier and sterilized by ebeam. Aftersterilization, the stent delivery system is optionally stabilized at 29°C. for 48 hours. The final stent material is substantially amorphouswith a percent crystallinity of less than approximately 25%. In oneexample, the intended deployment diameter is 3.0 mm. In another exampleit is 3.25 mm. In a third example it is 3.5 mm, and in a forth exampleit is 4.0 mm.

Example 11 Crystallinity of Tube or Stent Between 10%-50% afterModification

The tube is made by extrusion, a higher temperature than 75° C. is usedfor longer duration, wherein the crystallinity of polymeric materialafter treatment is between 10% and 50%.

A stent is patterned from a tube made from Poly(L-lactide-co-epsiloncaprolactone) material, preferably having a lactide to epsiloncaprolactone comonomer ratio of 85:15 to 95:05. The tube can be formedby extrusion. Before crimping, the tube or the stent has an innerdiameter that is 90 to 150% of the intended stent deployment diameter.As a further example, for an intended deployment diameter of at least 3mm stent, the tube inner diameter can range from 2.7 millimeter (0.106″)to 4.5 millimeter (0.177″). Another example is a 3.5 mm stent. The tubeinner diameter can range from 3.15 millimeter (0.124″) to 5.25millimeter (0.207″). The tube is heat treated at 180° C. for 2 hours andquenched to at or below ambient temperature. The tube is patterned intoa stent, coated with a drug matrix such as Poly(L-lactide) basedcopolymer and Novolimus. The coated stent is optionally vacuumed for 36hours at approximately 1 torr. The stent is then crimped at 40° C. ontothe balloon of a delivery catheter. The stent delivery system ispackaged in a sterile barrier and sterilized by ebeam. Aftersterilization, the stent delivery system is optionally stabilized at 25°C. for 5 hours. The final stent material has crystallinity less than 50%(optionally between 0 and 50%). The stent is radially expandable at bodytemperature.

Example of a stent capable to expand to at least 130% or 1.3 times anintended deployment diameter while keeping an intact stent structureintegrity and optionally having a recoil of less than 15% from anexpanded state (optionally less than 10%, or less than 5%) is shownherein.

Example 12 Crystallinity of Stent Lower than Crystallinity of the FormedTubular Body

The tube is made by extrusion, wherein the crystallinity of polymericmaterial after forming is between 30% and 55%. The stent is treated andis patterned from a tube made from Poly(L-lactide-co-epsiloncaprolactone) material, preferably having a lactide to epsiloncaprolactone comonomer ratio of 85:15 to 95:05. The tube can be formedby extrusion. Before crimping, the tube or the stent has an innerdiameter that is greater than the intended deployment diameter to 150%of the intended stent deployment diameter. As a further example, for anintended deployment diameter of at least 3 mm stent, the tube innerdiameter can range from greater than 3.0 millimeter to 4.5 millimeter.Another example is a 3.5 mm stent. The tube inner diameter can rangefrom greater than 3.5 millimeter to 5.25 millimeter. The tube is heattreated at 90° C. for 2 hours and quenched to below ambient temperature.The tube is patterned into a stent, coated with a drug matrix such asPoly(L-lactide) based copolymer and Novolimus. The coated stent isoptionally vacuumed for 36 hours at approximately 1 torr. The stent isthen crimped at 45° C. onto the balloon of a delivery catheter. Thestent delivery system is packaged in a sterile barrier and sterilized byebeam. After sterilization, the stent delivery system is optionallystabilized at 25° C. for 5 hours. The stent material has crystallinityless than 30%. The stent is radially expandable at body temperature andhas sufficient strength.

Example 13 Stent or Tube with the Ability Expand Above 1.3 TimesIntended Deployment Diameter, while Maintaining Structural Integrity orNo Breakage (Fracture) in the Struts, Links, or Crowns

A tubular stent is made as described above and at the end state thestent is expanded under physiologic conditions (or 37° C. in water)unconstrained or constrained inside a tube and expanded to 1.3 times thelabeled or intended deployment diameter without breakage/fracture in anyof the stent struts, links, or crowns.

A stent is patterned from a tube made from Poly(L-lactide-co-epsiloncaprolactone) material, preferably having a lactide to epsiloncaprolactone comonomer ratio of 82:18 to 98:02, more preferably at 88:12to 92:08. The tube can be formed by extrusion, molding, dipping, orspraying. The glass transitional temperature, Tg, of the polymericmaterial is greater than approximately 35° C. and less thanapproximately 55° C. Before it is patterned into a stent or before it iscrimped, the tube has an inner diameter of 0.9 to 1.5 times an intendeddeployment diameter. As an example, for an intended deployment diameterof at least 3 mm stent, the expanded inner diameter is between 2.7millimeter (0.106″) to 4.5 millimeter (0.177″). For a 3.5 mm stent, theexpanded inner diameter is between 3.15 millimeter (0.124″) to 5.25millimeter (0.207″). The tube is treated below the Tg of the material,ranging from 40° C. to 55° C., or heated at a temperature between theglass transitional temperature and its ambient temperature. A mandrelabout the size of the inner diameter of the tube or the stent or smalleris optionally placed inside the tube and the tube is optionally heatedabove the Tg of the material or optionally treated below Tg of thematerial for duration ranging from a fraction of a second to 5 hours.The tubing can either be slowly cooled or quickly quenched quickly to atemperature below the crystallization temperature or the glasstransitional temperature.

For example, an extruded tubing is made from 90:10Poly(L-lactide-co-epsilon-caprolactone) material. The tube is expandedfrom an inside diameter of 1 millimeter (0.041″) to 3.1 millimeter(0.122″) at a temperature of 100° C. A 3 millimeter mandrel is placedinside the expanded tube. The tube on a mandrel is placed in an oven at70° C. for a duration of about 1 hour. After heating, the tube isallowed to cool slowly to ambient temperature. The tube is patternedinto a stent. The stent is coated with a drug matrix consisting ofPoly(L-lactide) based copolymer and a macrocyclic lactone drug such asNovolimus. The coated stent is placed in a vacuum for a total of 36hours. It is then heated to a 70° C. which is above the Tg of thePoly(L-lactide) based copolymer coating for approximately 15 to 30minutes. The coated and treated stent is then crimped onto a ballooncatheter at a temperature below the glass transitional temperature ofthe stent material, preferably between 10° C. to 40° C. below the Tg ofthe stent material. After crimping, the stent delivery system ispackaged in a sterile barrier (i.e., in a foil pouch) and sterilized byebeam or cold ethylene oxide cycle. The stent delivery system is thenplaced in an oven or incubator at 25° C. to 30° C. for 24 to 168 hours,preferably at 29° C. for 48 hours. The stent can then be deployed to orabove 130 percent of an intended deployment diameter withoutfracture/breakage of stent struts, links, or crowns under physiologicconditions or in a simulated conditions unconstrained or constrainedwithin a tube. The stent is expandable at body temperature andoptionally have recoil of less than 15% from an expanded condition. Inthis example, 15% recoil is the mean recoil measurement.

Example 14 Physical Properties of a Bioresorbable Polymeric Stent

The physical properties of a biodegradable material of claimed inventionstent was compared to a bare metal stent in the following manner:

A. Example of Radial Strength (Radial Compression) Measurement

The test specimen is placed into a fixture which applies radialcompression. The fixture has compression dies or blades that areoriented in an iris-like configuration. These blades are actuated by atensile force measurement machine through a mechanical linkage connectedto a force gauge, which varies the opening of the fixture. The forceversus displacement is constantly measured. The force is normalized to aforce per unit measurement so that test specimens of various designs anddimensions may be conveniently compared. Other means to measure radialcompression can be applied as well. Radial strength examples can be themean value measurement of radial strength for multiple samples or asingle measurement of radial strength for a single sample.

B. Recoil

This is one example of measuring recoil. Other measurement techniquescan apply as well. The test specimen is expanded per the instructionsfor use and the diameter is measured at one or more locations while thedevice is inflated (Diameter-Initial) using an appropriate instrument.The test specimen is then measured at similar locations at one or moretime intervals after device deflation (Diameter-Final), and the recoilis calculated as the percent change in diameter, or(Diameter-Initial−Diameter-Final)/Diameter-Initial*100%. As one skilledin the art, recoil can be measured using various method for benchtesting of recoil, QCA measurement for recoil, OCT measurements forrecoil. An example of recoil is a single measurement at a singlelocation, or mean measurement at a single or multiple locations for thesame stent.

C. Crimped Flexibility and Expanded Conformability

In this example, the test specimen is placed into a fixture whichapplies a 3 point bend load. The test specimen may be as-manufactured orprepared in a clinically-relevant manner, such as soaking the device influid at body temperature prior to testing, or expanding the device perthe instructions for use. The 3 point bend fixture has a span that is afixed distance appropriate for the sample, such as 13 mm of a samplethat is greater than 13 mm. An anvil is aligned to the center of thespan and connected to the force gauge on a tensile force measurementmachine, which lowers the anvil and in turn applies a force to the testspecimen, which is centered across the span. The force versusdisplacement is constantly measured to a fixed displacement, such as 15%of the span. The force per unit displacement is calculated.

The results are shown in FIGS. 13 and 14. BDES stands for bioresorbable,drug eluting stent, while BMS stands for bare metal stent.

D. In Vitro Testing

FIG. 15 shows an example of in vitro testing of an expanded sample stentto approximately 3.0 mm internal diameter (ID) with an outer diameter(OD) of about 3.3 mm (prior to approximately less than 10% recoil froman expanded state). The stent diameter is at least maintained or growsover time (approximately within 15 days) to approximately at least 3.0mm and substantially maintain the stent over a period of time such asover 1 month, 2 month, 3 month, or 4 months. This experiment wasconducted in a saline tube submerged in a water bath at 37° C. Thediameters of the stents were measured at approximately the middle of thestent using an optical comparator.

FIG. 16 shows an example of in vitro testing for MW over time for designA and design B submerged in a saline at 37° C. showing MW decreasingover time. MW was measured using GPC. Design A and Design B were stentswith different patterning designs and treatments.

FIG. 17 shows an example of in vitro testing of sample design A anddesign B submerged in a saline at 37° C. showing that the stent radialstrength after expansion of the stent increases by at least 5%, or atleast 10%, or at least by 15% over time (within approximately 30 days orwithin approximately 15 days) and maintains sufficient strength tosupport a body lumen for at least one month, or at least two months, orat least three months, or at least four months. A stent deployed tonominal diameter increased in strength over initial period followed by adecrease in strength. Radial strength was measured using the radialcompression iris method. FIG. 18 shows a stent balloon expanded toaround 3.6 mm OD wherein the stent further self expands within one hourby at least 0.1 mm.

Example 15 Biodegradable Stent

A stent is patterned from a tube made from Poly(L-lactide-co-epsiloncaprolactone) material blended with 0.1%-10% by weight ratiopolyglycolide polymer or glycolide monomer, preferably having a lactideto epsilon caprolactone comonomer ratio of 82:18 to 98:02 blended with0.1%-10% polyglycolide or glycolide by weight ratio, more preferably at88:12 to 92:08 and 5% or under by weight ratio polyglycolide polymer orglycolide monomer. The tube can be formed by extrusion, molding,dipping, printing, or spraying. The glass transitional temperature, Tg,of the polymeric material optionally is greater than approximately 35°C. and less than approximately 55° C. Before it is patterned into astent or before it is crimped, the tube has optionally an inner diameterof 0.9 to 1.5 times an intended deployment diameter. As an example, foran intended deployment diameter of at least 3 mm stent, the expandedinner diameter is between 2.7 millimeter (0.106″) to 4.5 millimeter(0.177″). For a 3.5 mm stent, the expanded inner diameter is between3.15 millimeter (0.124″) to 5.25 millimeter (0.207″). The tube istreated below the Tg of the material, ranging from 40° C. to 55° C., orheated at a temperature between the glass transitional temperature andits ambient temperature, or treated by heat above Tg. A mandrel aboutthe size of the inner diameter of the tube or the stent or smaller isoptionally placed inside the tube and the tube is optionally heatedabove the Tg of the material or optionally treated below Tg of thematerial for duration ranging from a fraction of a second to 5 hours.The tubing can either be slowly cooled or quickly quenched quickly to atemperature below the crystallization temperature or the glasstransitional temperature. The stent prosthesis is crimped onto adelivery system. The stent is capable of radial expansion underphysiologic environment and/or 37 C to a deployed diameter from acrimped diameter. The stent has sufficient strength to support a bodylumen at an expanded diameter, the stent optionally has % acute recoilof under 10%, the stent substantially degrades under 2 years, preferablysubstantially degrades under 1.5 years.

A tubular stent is made as described above and at the end state thestent is expanded under physiologic conditions (or 37° C. in water)unconstrained or constrained inside a tube and expanded to >1.1 timesthe labeled or intended deployment diameter without breakage/fracture inany of the stent struts, links, or crowns.

A. In Vitro Testing, Diameter, Strength, and Degradation Study

A stent prosthesis was fabricated in accordance with an embodiment ofthe invention. Samples of three designs were produced and expanded to adeployed diameter using indeflator. An initial diameter measurement wastaken and strength was measured at time zero. The units were tested inenvironment simulating physiologic environment (and/or 37 C in water)such as placed into a single capped 250 mL bottle filled with saline(0.85% Sodium Chloride solution, Sigma Aldrich) and maintained at 37° C.in a static water bath for the duration of the test. At regularintervals the diameter, strength, and molecular weight were measured.FIGS. 19A and 19B show balloon expanded stents at least maintain thediameter of tubular stents of design A, design B, and design C, overtime (1 month and 6 months, respectively). FIG. 20 shows changes in thestrength of tubular stents of design A, design B, and design C overtime.

B. Scaffold Implantation in Porcine Model

The scaffold was implanted in the internal mammary artery in a porcinemodel per standard implantation techniques. The scaffold and the arterywere explanted at different timepoints and the scaffold materialmolecular weight was measured using analytical techniques.

The scaffold molecular weight decreases by 50% in less than six months.The molecular weight decreases to less than 25% in less than 6 months.The molecular weight decreases to less than 10% in less than 18 months.

The in vitro and in vivo molecular weight over time was plotted on agraph and demonstrated that the in vitro and in vivo degradation wassimilar. FIGS. 21A and 21B show the decrease of molecular weight ofstent over one to two years with radial strength sufficient to support ablood vessel for at least 2 months.

C. Underdeployed Stent Scaffold Apposition Testing

A sample unit of the present invention was underdeployed in a mockartery, which was a plastic block with a 3.2 mm hole. The scaffolddiameter was recorded as 3.12 mm Backlighting was employed to visuallyidentify gaps between the scaffold outer diameter and the block innerdiameter. The block with the scaffold in the hole was then placed in a37° C. water bath and the presence of gaps was noted. After 5-10minutes, the gaps were no longer present. The scaffold was removed andmeasured to be equal or greater than 3.2 mm, confirming that themalapposition between scaffold and mock artery fixture had beenresolved. FIG. 22A illustrates a stent scaffold deployed in a block,with a final diameter smaller than block simulating malapposed struts.FIG. 22B illustrates stent scaffold within 5-10 minutes of soaking inwater at 37° C., with gaps “resolved” and no longer present. The exampleshows a balloon expanded stents, where in the stent further self expandsto a larger diameter or transverse dimension, or until the stent apposesthe vessel wall.

D. Scaffold Strut Malapposition Testing

A sample unit of the present invention was deployed in a mock artery,which was a plastic block with a 3.2 mm hole, with a 0.3 mm mandrel onone side creating an eccentric deployment cross-section. The mandrel wasremoved and created a malapposition between the scaffold and the surfaceof the mock artery. Backlighting was employed to visually identify thegap between the scaffold and the block inner diameter. The block withthe scaffold in the hole was then placed in a 37° C. water bath and thepresence or absence of the malapposition was noted over time. After 20minutes, the gap was no longer visually present. FIG. 23A illustrates astent scaffold expanded in a mock artery with a 0.3 mm mandrel on theside. FIG. 23B illustrates a stent scaffold with mandrel removed,confirming that a gap is still present. FIG. 23C illustrates a stentscaffold shows a stent scaffold after 10 minutes of soaking in water,and FIG. 23D illustrates a stent scaffold after 20 minutes of soaking inwater where in the stent is apposed against the vessel wall. This alsoprovides an example of stent strut self expanding to appose against thevessel wall during a side branch treatment procedure of kissing balloontechnique where in the guidewire has to be pulled out from under theexpanded stent in the vessel leaving behind unapposed struts. The Stentstruts in the present invention after the procedure will self expand byat least 0.1 mm and appose to the vessel wall.

E. Scaffold Overexpansion Study

Sample units of the present invention were deployed in a 37° C. waterbath to nominal diameter of 3.0 mm using standard inflation techniques.The scaffolds were then post-dilated to multiple diameters and inspectedat regular intervals until a fracture was noted. The diameter atfracture was recorded. Pictures were also taken at regular intervals. Bytesting several units, the number of units with fractures at a givendiameter was calculated and plotted. FIG. 24 shows a plot illustratingthe likelihood of fracture against post-dilated scaffold diameter for(e.g., a balloon expanded stent at nominal diameter of 3.0 mm andfurther balloon expanded to 4.8 mm diameter, 1.6 times the nominaldeployed diameter, survives without fracture). FIG. 25A depicts ascaffold at 3.0 mm nominal diameter, and FIG. 25B depicts a scaffolddeployed at nominal and further balloon expanded at 3.8 mm overexpandeddiameter. FIG. 25C depicts a scaffold deployed at nominal and furtherballoon expanded to 4.0 mm overexpanded diameter, FIG. 25D depicts ascaffold deployed at nominal and further balloon expanded to 4.4 mmoverexpanded diameter, FIG. 25E depicts a scaffold deployed at nominaland further balloon expanded to a 4.75 mm overexpanded diameter, andFIG. 25F depicts a scaffold deployed at nominal and further balloonexpanded to a 5.1 mm overexpanded diameter. The figures shows theundulating rings of the stent overexpanded to substantially circularrings without fracture.

Example 16 Bioresorbable Polymeric Stent+Myolimus @ 3 μg Per mm StentLength (DESolve First in Man Study)

The DESolve I trial is a first in man study enrolling 15 patientsevaluating the Myolimus Eluting Bioresorbable Coronary Scaffold System(CSS) with a PLLA based polymer. The principal imaging endpointsinclude: in-stent late lumen loss assessed by QCA at 6 months, stent andvessel assessment using IVUS, OCT at baseline and 6 months, andmulti-slice computed tomography (MSCT) at 12 and 24 months to providelong-term assessment of the vessel. The principal safety endpoint is thecomposite of major adverse cardiac events (MACE) comprised of cardiacdeath, target vessel myocardial infarction (MI) and clinically-indicatedtarget vessel revascularization (TLR) at 30 days, 6, 12 months, and 2-5years. The stent size used is 3.0×14 mm and myolimus drug dose is 3 μgper mm of stent length. A portion of the available results as measuredand analyzed by the principal investigators lab are shown in the Table14 below A complete analysis of the results from the core laboratory arepresented later in Part II.

A. Stent or Tube with the Ability Expand Above 1.1 Times DeploymentDiameter, while Maintaining Structural Integrity or No Breakage/Fracturein the Struts, Links, or Crowns; and have Accelerated Degradation PeriodBelow 2 Years, Preferably Below 1 Year

TABLE 14 Acute stent recoil in the DESolve ™ I group of patients nNumber of patients 12 Age (years) 72.0 ± 6.9  Gender (males) 6 (50%)Target vessel 12 LAD 2 (20%) LCX 4 (30%) RCA 6 (50%) Stent size (mm) 3.012 (100%) Stent length (mm) 14 12 (100%) Maximum pressure (atm) 13.7 ±2.5  Predicted ID (mm) 3.2 ± 0.1 QCA measurements Pre-PCI Referencevessel diameter (mm) 2.5 ± 0.5 Minimum lumen diameter (mm) 1.1 ± 0.3Diameter stenosis (%) 49.2 ± 13.8 Post-PCI Reference vessel diameter(mm) 2.6 ± 0.5 Minimum lumen diameter (mm) 2.1 ± 0.3 Diameter stenosis(%)  9.0 ± 10.5 Last inflated balloon at the highest pressure MinD (mm)2.1 ± 0.4 Last inflated balloon at the highest pressure MaxD (mm) 2.9 ±0.2 Last inflated balloon at the highest pressure MeanD (mm) 2.6 ± 0.3(X) Stent immediately after last balloon MinD (mm) 2.1 ± 0.3 Stentimmediately after last balloon MaxD (mm) 3.0 ± 0.4 Stent immediatelyafter last balloon MeanD (mm) (Y) 2.6 ± 0.3 IVUS post-interventionmeasurements at MSA site IVUS MinSD (mm) 2.1 ± 0.3 IVUS MaxSD (mm) 2.8 ±0.3 IVUS MeanSD (mm) 2.5 ± 0.2 IVUS MSA(mm²) 4.7 ± 0.8 OCTpost-intervention measurements at MSA site OCT MinSD (mm) 2.1 ± 0.4 OCTMaxSD (mm) 2.9 ± 0.5 OCT MeanSD (mm) 2.5 ± 0.4 OCT MSA (mm²) 5.0 ± 1.5Recoil calculations Acute absolute recoil QCA (X − Y) 0.02 ± 0.2  Acutepercent recoil QCA (X − Y)/X (%) 0.8 ± 8.9 IVUS MinSD/predicted ID ratio0.60 ± 0.2  OCT MinSD/predicted ID ratio 0.66 ± 0.1 

The mean acute absolute recoil measurement by QCA in the example abovewere calculated using the measurement technique as described in Tanimotoet al, CCI 70:515-523 (2007).

Example 17 Clinical Trial Data for DESolve Study

FIGS. 26A and 26B depict the DESolve™ Bioresorbable Coronary StentScaffold used in the DESolve 1 clinical trial. FIG. 27 depictspreclinical optical coherence tomography (OCT) images of the scaffold atdifferent time points. FIG. 28 schematically depicts the DESolve™First-in-Man (FIM) study design.

Table 15 describes patient characteristics and angiographic results.FIG. 29 depicts Intravascular Ultrasound (IVUS) results from theDESolve™ FIM study. FIG. 30 depicts the methodology of OCT analysiswhere NIH stands for neointimal hyperplasia.

TABLE 15 Baseline and angiographic characteristics and angiographicresults at baseline and 6 month follow-up in patients BaselineCharacteristics Patient Characteristics, % (n) (n = 15 Patients*) Age,years (±SD) 70 ± 8.6 Male 66.7 (10/15) Diabetes mellitus 6.7 (1/15)Current/former smoker 7.33 (11/15) Hypercholesterolemia 7.33 (11/15)Hypertension 66.7 (10/15) Previous myocardial infarction 26.7 (4/15) Previous target vessel CABG or PCI 6.7 (1/15) AngiographicCharacteristics Baseline Characteristics, % (n) n = 14 (paired) RVD (mm)2.65 ± 0.32 MLD (mm) 0.81 ± 0.29 % DS 70.0 ± 10.5 Lesion Length (mm)8.95 ± 2.64 Target Vessel, % (n) LAD 21.4 (3/14) LCX 35.7 (5/14) RCA42.9 (6/14) Lesion Class (ACC/AHA), % (n) A 35.7 (5/14) B1/B2 64.3(9/14) C  0.0 (0/14) Angiographic Results In-scaffold Analysis n = 14(paired) RVD (mm) post-procedure 2.84 ± 0.23 at 6 months 2.78 ± 0.27 MLD(mm) post-procedure 2.60 ± 0.19 at 6 months 2.41 ± 0.28 % DiameterStenosis post-procedure 8.05 ± 7.90 at 6 months 12.63 ± 11.37 AcuteRecoil (%) 6.4 ± 4.6 Late Lumen Loss (mm) at 6 months 0.19 ± 0.19 BinaryRestenosis (%) at 6 months 0.0

Table 16 includes OCT results of the DESolve FIM Study. The results showthe mean scaffold area was maintained between baseline and 6 month.There was minimal neointimal growth leading to a low % neointimalobstruction within the vessel lumen. Table 17 includes clinical outcomesof the DESolve FIM study at 0 to 30 days. Table 18 includes clinicaloutcomes of the DESolve FIM study at 31 to 180 days showing clinicalsafety of the DESolve scaffold.

TABLE 16 DESolve FIM: OCT Results 6-month Baseline Follow-up n = 10(paired) In-scaffold Cross Section Level Serial Analysis Mean Scaffoldarea (mm²) 6.57 ± 0.68  6.80 ± 0.85* Mean NIH Area (obstructive) (mm²) —0.71 ± 0.36 Mean NIH Obstruction (%) — 13.16 ± 5.59  In-scaffold StrutLevel Serial Analysis Total number of Analyzed Struts 2,984 2,575Frequency of covered Struts/patient (%) — 98.68 ± 2.44  Mean NIHThickness over Covered — 0.12 ± 0.04 Struts (mm) *p = ns betweenbaseline and follow-up

TABLE 17 Clinical Outcomes: 0 to 30 days. 0 to 30 days (n = 15)Hierarchical Events, % (n) Cardiac Death 0/15 Target Vessel MI 0/15Clinically-Indicated TLR 0/15 Major Adverse Cardiac Events 0/15 OtherEvents Stent Thrombosis (ARC^(∫)) 0/15 Definite 0/15 Probable 0/15Clinically-Indicated TVR   1/15 ^(§) ^(§) one patient underwent emergentCABG for a procedurally-related spiral dissection; there was no stentthrombosis in the scaffold area or within the 5 mm segment proximal ordistal to the scaffold ^(∫)Cutlip, D, Windecker, S, Mehran, R, et al.Clinical Endpoints in Coronary Stent Trials: A Case for StandardizedDefinitions. Circ 2007; 115; 2344-2351

TABLE 18 Clinical Outcomes: 31 to 180 days. 31 to 180 days (n = 15)Hierarchical Events, % (n) Cardiac Death 0/15 Target Vessel MI 0/15Clinically-Indicated TLR  1/15* Major Adverse Cardiac Events 1/15 OtherEvents Stent Thrombosis (ARC^(∫)) 0/15 Definite 0/15 Probable 0/15Clinically-Indicated TVR 0/15 *one patient underwent PCI for a stenosisin the proximal 5 mm segment to the scaffold; the scaffold area waswidely patent ^(∫)Cutlip, D, Windecker, S, Mehran, R, et al. ClinicalEndpoints in Coronary Stent Trials: A Case for Standardized Definitions.Circ 2007; 115; 2344-2351

Example 18 Stent Fabrication

A tube is made by spraying an amorphous copolymerpoly(L-lactide-co-glycolide) with 85% lactide and 15% glycolide. Thepolymer and rapamycin analog can be dissolved in a solvent and can besprayed together to incorporate the rapamycin into the polymer stent. Amandrel is placed underneath an ultrasonic spray nozzle (MicromistSystem with Ultrasonic Atomizing Nozzle Sprayer, Sono-Tek, NY) which isrotating at 80 rpm and move longitudinally at a rate of 0.050inches/minutes. A solution of 11 to 1 ratio ofpoly(L-lactide-co-glycolide) and rapamycin analog on the mandrel. Theresulting tube has a thickness of 0.17 mm. The tube is heated at 45° C.for about 60 hours, annealed at 90° C. for 2 hours, and cooled toambient or room temperature within 10 seconds. The annealed tube is thencut with a UV laser to the design shown in FIG. 34 (shown in its crimpedstate). The cut stent is annealed at 90° C. and slowly cooled from theannealing temperature to ambient temperature within eight hours. Thestent delivery system is then packaged in a pouch and sterilized bygamma radiation.

The heat treated stent has higher radial strength than the non-treatedstent (Table 19).

TABLE 19 Comparison of Radial Strength of Treated and Non-treated Stent.No Heat Heat Type Treatment Treatment Radial Strength After LaserCutting Stent 7 Psi 14 Psi  Radial Strength After Crimping Stent 6 Psi 9Psi Radial Strength After 30 kGy Ebeam 3 Psi 8 Psi Sterilization RadialStrength when expanded at Tg n/a 12.5 Psi  

Thus, as shown in FIG. 31, methods according to the present inventioninitially provide for a tubular body comprised of an amorphous polymer,where the tubular body may be formed by extrusion, molding, dipping, orthe like, but is preferably formed by spraying onto a mandrel. Thetubular body is annealed to increased crystallinity and strength,usually by the heating and cooling processes described above. Thetubular body is then patterned to form a stent or other endoprosthesis,typically by laser cutting, usually after at least one annealingtreatment. Optionally, the tubular body may be treated both before andafter patterning, and may be treated by annealing more than once bothbefore and after the patterning.

Referring now to FIGS. 32A and 32B, a stent 10 suitable for modificationby the present invention has base pattern including a plurality ofadjacent serpentine rings 12 joined by axial links 14. As illustrated,the stent 10 includes six adjacent serpentine rings 12, where each ringincludes six serpentine segments comprising a pair of axial struts 16joined by a hinge-like crown 18 at one end. The number of rings andsegments may vary widely depending on the size of the desired size ofthe stent. According to the present invention, a supporting feature 20is disposed between adjacent axial struts 16 and connected so that itwill expand, usually elongate, circumferentially with the struts, asshown in FIG. 3. The supporting features 20 are in a generally closedU-shaped configuration prior to expansion, as shown in FIGS. 32A and32B, and open into a shallow V-shape along with the opening of the axialstruts 16 about the crowns 18 during radial expansion of the serpentinerings 12, as shown in FIG. 33. Supporting features 20 enhance the hoopstrength of the stent after radial expansion, help resist recoil afterexpansion is completed, and provide additional area for supporting thevascular or other luminal wall and optionally for delivering drugs intothe luminal wall.

Example 33 Novolimus Eluting Bioresorbable Stent in a Clinical Trial

DESolve Nx was a prospective, multicenter international trial evaluatingthe DESolve Nx Novolimus Eluting Coronary Scaffold System of the presentinvention. The trial was conducted at 13 international centers acrossEurope, Brazil and New Zealand with enrollment of 126 patients. Thetrial was designed to evaluate single de novo coronary artery lesionswith a reference vessel diameter between 2.75 and 3.0 mm and lesionlength <12 mm Scaffold sizes available were 3.0, 3.25, 3.5 mm diametersand 14 and 18 mm lengths. Study follow up for clinical events wasscheduled for 30 days, six months, 12 months and yearly until fiveyears. Imaging endpoint assessments were planned for six month follow up(QCA for all patients and intravascular ultrasound (IVUS) OCT in asubset of patients) and 12 month follow up (Multislice computedtomography (MSCT) in a subset of patients).

The primary endpoint of the study was in-scaffold late lumen lossassessed at the six month time point. Key secondary endpoints included:

Clinical: (30 days, 6 m, 12, 2-5 years)

-   -   MACE (Major Adverse Cardiac Events) a composite of Cardiac        Death, Target Vessel MI or Clinically-Indicated Target Lesion        Revascularization    -   Scaffold Thrombosis

QCA (6 m)

-   -   In Segment late lumen loss    -   Binary Restenosis    -   % Diameter Stenosis

IVUS (6 m)

-   -   In scaffold % Volume Obstruction    -   Malapposition

OCT (6 m)

-   -   In scaffold % obstruction    -   Strut Coverage

MSCT (12 m)

-   -   % DS    -   Lumen Area

Patient Disposition and Follow Up:

A total of 126 patients (126 lesions) were enrolled. 6 m follow up wasavailable on:

-   -   Clinical Follow Up: 120 patients (98%)    -   Serial QCA Follow Up: 113 patients (92%)    -   Serial IVUS Subset Follow Up: 40 patients (87%)    -   Serial OCT Subset Follow Up: 38 patients (83%)

Key Baseline Characteristics:

TABLE 21 Patient Characteristics, % unless stated N = 126 Age, years(mean ± SD) 62.0 ± 9.8 Male 68.3% Diabetes mellitus 21.4%Hypercholesterolemia 70.6% Hypertension 70.6% Previous MI 44.4% PreviousPCI 35.7% Unstable Angina 12.7%

Patient Characteristics,

% unless stated N = 126 Age, years (mean ± SD) 62.0 ± 9.8 Male 68.3%Diabetes mellitus 21.4% Hypercholesterolemia 70.6% Hypertension 70.6%Previous MI 44.4% Previous PCI 35.7% Unstable Angina 12.7%

Lesion Characteristics (QCA):

TABLE 22 N = 126 Lesion Characteristics N_(L) = 126 Target-vessel LAD28% (48) LCX 31% (39) RCA 31% (39) Calcium (moderate/severe) 18% (23)Eccentricity 44% (55) Pre-TIMI 3 flow  97% (122) Lesion length, mm 11.20± 3.77  Reference diameter (int.), mm 3.06 ± 0.31 MLD, mm 0.92 ± 0.40 %DS 69.9 ± 12.3 N = 126 N_(L) = 126

Target-Vessel

LAD 28% (48) LCX 31% (39) RCA 31% (39) Calcium (moderate/severe) 18%(23) Eccentricity 44% (55) Pre-TIMI 3 flow  97% (122) Lesion length, mm11.20 ± 3.77  Reference diameter (int.), mm 3.06 ± 0.31 MLD, mm 0.92 ±0.40 % DS 69.9 ± 12.3

6 m Clinical Outcomes:

TABLE 23 Hierarchical Events 0 to 180 days, n (%) (N = 122)* MajorAdverse Cardiac Events 3.28% Cardiac Death 1 (0.8%) (Probable ST) ⁺Target vessel MI ** 1 (0.8%) Q-wave MI 0 (0.0%) Non-Q- wave MI 1 (0.8%)Clinically Indicated-TLR PCI 2 (1.6%) Definite Stent Thrombosis⁺ 0(0.0%) *Modified Intent To Treat = those patients in which a scaffoldwas implanted; ⁺ ARC-defined; ST = stent thrombosis; **MI during followup attributed to multi modality imaging procedure.

6 m Diabetes Sub Analysis:

TABLE 24 Hierarchical Events Diabetes Non Diabetes 0 to 180 days, % (n)(N = 26)* (N = 96) Major Adverse Cardiac Events 1/26 3/96 Cardiac Death0 1/96 (Probable ST) * Target vessel MI ⁺ 1/26 0 Q-wave 0 0 Non-Q- wave 1/26⁺ 0 Clinically Indicated-TLR PCI 0 2/96 Definite Stent Thrombosis*0 0

Serial QCA Outcomes Post Procedure and at 6 m: (N=126, Post ProcedureN=113 at 6 m):

TABLE 25 Post-Procedure QCA Variable N = 126 IN-SCAFFOLD Referencediameter (int.), mm 3.09 ± 0.26 MLD, mm 2.67 ± 0.28 % DS 13.5 ± 7.8 Acute gain, mm 1.73 ± 0.45 IN-SEGMENT Reference diameter (int.), mm 3.04± 0.30 MLD, mm 2.59 ± 0.30 % DS 14.5 ± 7.9  Acute gain, mm 1.66 ± 0.44Balloon:artery ratio 1.11 ± 0.08 Values are presented as mean ± standarddeviation

TABLE 26 Acute Recoil: Measured at Post-Procedure (Final) AngiogramVariable N = 126 % Acute recoil 6.6 ± 6.2 Values are presented as mean ±standard deviation

TABLE 27 QCA at 6 Months FU Variable N = 113 IN-SCAFFOLD Referencediameter (int.), mm 3.01 ± 0.29 MLD, mm 2.45 ± 0.44 % DS 18.3 ± 13.6Late lumen loss, mm 0.21 ± 0.34 Median late lumen loss, mm*) 0.11 [0.04,0.21] IN-SEGMENT Reference diameter (int.), mm 2.98 ± 0.31 MLD, mm 2.34± 0.44 % DS 2.13 ± 13.0 Late lumen loss, mm 0.25 ± 0.34 BinaryRestenosis 3.5% (4) Values are presented as mean ± standard deviation orpercentage of total, median and interquartile range [25%, 75%]

TABLE 28 Edge Analysis Post-Procedure 6 - Month FU Variable N = 126 N =113 Proximal Edge MLD, mm 2.93 ± 0.36 2.70 ± 0.44 % DS 8.2 ± 7.3 13.1 ±10.4 Late lumen loss, mm — 0.22 ± 0.30 Distal Edge MLD, mm 2.77 ± 0.352.58 ± 0.38 % DS 7.0 ± 6.3 11.3 ± 8.8  Late lumen loss, mm — 0.20 ± 0.25Values are presented as mean ± standard deviation

FIG. 41 shows 6 m diabetes subset QCA outcomes.

FIGS. 42 and 43 show serial IVUS outcomes at baseline (post procedure)and at 6 m: (N=40).

FIG. 44 shows vessel, scaffold, and lumen areas and volumes.

FIG. 45 shows the distribution of % NIH obstruction.

FIG. 46 shows serial OCT outcomes at (scaffold and lumen area) baseline(post-procedure) and at 6 m: (N=38).

FIG. 47 is a series of IVUS/OCT images which provide a lumen areacomparison analysis

FIG. 48 provides a graphical lumen area comparison analysis.

Table 29 provides an incomplete scaffold apposition (ISA) analysis.

In-scaffold Strut Level N_(S) = 14.261 Analysis Baseline 6 m P value ISA(n) 15 5 ISA Area (mm²) 0.19 ± .015 0.35 ± .015* 0.33 N_(S) Number ofStruts; N_(L) Number of Lesions *One patient with post baseline ISA(area 0.30 mm²) due to resolution of thrombus visible on OCT

FIGS. 49 and 50 provides an NIH quantification by OCT.

FIGS. 51 and 52 provide an NIH thickness and distribution analysis.

FIGS. 53 and 54 provide a strut coverage (safety surrogate) analysis.

Example 19 Tapered Main Artery and Bifurcation

An artery may be tapered such that the proximal segment is larger indiameter than the distal segment. This typically occurs at a bifurcationof a main artery and a side branch. The current embodiment of the devicemay be expanded such that the sizing is appropriate for the distalsegment of the main artery, and somewhat smaller in diameter than theproximal segment of the main artery. In a normal balloon expandablescaffold or stent expanded in such a manner, the proximal segment wouldthen be malapposed to the vessel wall.

The malapposition may be resolved by expanding the proximal segment ofthe scaffold with a post-dilatation balloon to a larger diameterpositioned appropriately at the proximal segment. The current embodimentof the device has the ability to be expanded to a large diameter at theproximal segment such that the scaffold does not fracture.

Because the current embodiment of the device has the ability toself-expand over time, the malapposition would be resolved and thescaffold would self-appose to the artery wall.

For example, a scaffold is manufactured from a 4.0 mm tube. The scaffoldis deployed in an artery that is tapered from 3.5 mm to 2.75 mm(proximal to distal). The device is crimped onto a delivery system,delivered to the tapered deployment site, and expanded to 3.0 mm. The2.75 mm distal segment is well apposed, and the proximal 3.5 mm segmentis malapposed. The malapposition is resolved by either post-dilating theproximal segment with a larger 3.5 mm balloon without fracturing thescaffold, or allowed to resolve over a period of time by the ability ofthe device to self-resolve malapposition.

Example 20 Balloon Expansion Followed by Self Expansion

A biodegradable stent is fabricated from a polymeric sheet comprisinglactide-co-caprolactone (or a blend of lactide and caprolactone) whereinthe sheet is joined at its ends via solvent bonding, ultrasonic bonded,inductive heating bonded, or heat welding. The polymeric sheet has aninitial diameter of 4.5 mm. The stent is treated, and crimped withoutfracture onto a balloon catheter and sterilized at 30 kGy. Aftersterilization, the stent at body temperature is balloon expanded from acrimped configuration to a first expanded diameter of 3.5 mm and whereinthe stent further self expands to a second larger diameter of 3.75within 24 hours. The stent does not have fractures (completely brokenstruts) at the first or second expanded diameters and has sufficientstrength to support a body lumen. The stent is patterned before thesheet is joined or after.

Example 21 Self Expansion Followed by Balloon Expansion

A biodegradable stent comprising a polymeric material comprisinglactide-co-glycolide (or a blend of lactide and glycolide) which ismolded into an initial diameter that is 0.9-1.5 times thenominal/labeled deployed stent diameter. The initial diameter is 4.5 mmand the nominal deployment/labeled diameter is 3.5 mm. The stent iscrimped to a smaller diameter of about 1.5 mm onto a catheter withoutfracture and sterilized at 30 kGy. The stent at body temperature (about37 C) self expands from the crimped configuration to a first expandeddiameter of about 3.75 mm within about 30 minutes and further expandedby balloon to a second expanded diameter of 4.75 mm without fracture andhave sufficient strength to support a body lumen. The stent is patternedby the mold or after the mold or the mold forms a tubular body that issubsequently patterned.

Example 22 Incorporation of at Least One Solvent to Allow Expansion of aStent without Fracture

A biodegradable stent comprising a polymeric material formed into atubular body wherein the polymeric material compriseslactide-co-caprolactone (or a blend of lactide and caprolactone). Thetubular body is formed by spraying the polymeric material onto amandrel. DCM is incorporated into the solution to such that the amountof DCM after treatment is 1.5% by weight of the polymeric material. Thetubular body is treated, is patterned, and is crimped onto a deliverysystem without fracture and sterilized. The stent at body temperature(about 37 C) is expandable from the crimped configuration to an expandeddiameter that is 1.2 times the nominal deployment diameter (labeleddiameter) of the stent without fracture and having sufficient strengthto support a body lumen.

Example 23 Incorporation of Monomer in Amounts Sufficient to AllowExpansion of the Stent without Fracture

A biodegradable stent is formed by 3-D printing of polymeric materialcomprising polylactide-co-glycolide blended with about 30000 ppm ofε-caprolactone monomer. The stent is treated and crimped to a smallerdiameter of about 1 mm without fracture, and sterilized. The stent atbody temperature is expanded from the crimped configuration to theexpanded diameter of nominal or higher without fracture and havingsufficient strength to support a blood vessel.

Example 24 Crimping without Fracture

A biodegradable stents having the pattern of FIG. 1 were laser cut frompolymeric tubes made by spraying polymeric material comprisingpoly(L-lactide-co-ε-caprolactone) copolymers or blends and treated, andpatterned into stents. Five stents having an initial inner diameter of2.5 mm are subjected to crimping at 45° C. After crimping, the innerdiameters of the stents are 2.0 mm, 1.8 mm, 1.4 mm, 1.6 mm, and 1.2 mm,1.0, 0.8 mm respectively. None of the five stents exhibit significantcracks or any fractures.

Example 25 Pressure Treatment to Control Crystallinity

A biodegradable stent comprising a polymeric material is formed byspraying a solution of 85% L-lactide to 15% glycolide onto a mandrel.The material has crystallinity of 40% The material is then placed in ahigh pressure stainless steel vessel, sealed, and subjected to carbondioxide at a pressure of 700 psi for 24 hours. After the exposure tocarbon dioxide, the crystallinity is about 25% by XRD.

Example 26 Expansion of a Biodegradable Stent Above Nominal Deploymentwithout Fracture

A biodegradable stent comprising poly(L-lactide-co-ε-caprolactone)polymer is molded into a tubular body, is treated, and is patterned. Thestent has an initial diameter of 3.8 mm. The stent is crimped to a 1 mmdiameter without fracture and mounted on a 3.0 mm nominal/labeledballoon of a catheter and sterilized at 30 kGy. The stent at bodytemperature is balloon expanded to above the nominal/labeled deploymentdiameter of 3.0 mm by expanding it to 4.8 mm without fracture and havesufficient strength to support a blood vessel.

Example 27 Drug Incorporation into the Polymeric Material or TubularBody for Extended Delivery

180 mg Poly-DL-lactide is dissolved in 60 ml of dichloromethane and 1 mgof rapamycin is added to the solution. The mixture is mixed for 10minutes. The mixture is then sprayed onto a mandrel to form a tubularbody. After dichloromethane evaporates, the mandrel is removed from thetube and tube is allowed to air-dried for 48 hours. The tubular body ispatterned into a stent. The stent is crimped without fracture andmounted on a balloon of a catheter and sterilized at 30 kGy. The stentbody temperature is expanded from a crimped configuration to deliver thedrug over an extended period of time between 3 months and 2 years.

Example 28 Treatment to Control of One or More of Crystallinity, Tg, andM_(W)

A biodegradable stent as in any of the examples from A though H whereinthe polymeric material is treated to control at least one ofcrystallinity, Tg, or MW, wherein the crystallinity ranges from 1% to50%, Tg ranges from >37 C to 50 C, and MW ranges from 30 Kda to 700 Kdawherein the stent is capable to be crimped and expanded from a crimpedcondition to a deployed condition without fracture and have sufficientstrength to support a body lumen.

Example 29 Biodegradable Stent Properties

A biodegradable stent as in Examples 20 through 28 comprising apolymeric material wherein the material has at least one of elasticmodulus of 0.35 GPa or higher, strength of 2 psi or higher, recoil froman expanded diameter of 10% or less; wherein the stent is capable to becrimped from an expanded condition to a crimped condition withoutfracture and wherein the stent is capable at body temperature to beexpanded to nominal diameter or higher without fracture.

The invention provides polymeric materials, including biodegradablestents, and methods of their fabrication. Various aspects of theinvention described herein may be applied to any of the particularapplications set forth below or in any other type of setting. Theinvention may be applied as a standalone system or method, or as part ofan integrated system or method. It shall be understood that differentaspects of the invention can be appreciated individually, collectively,or in combination with each other.

Numerous modifications, variations, alternatives and equivalents to thepresent disclosure, as set forth in the embodiments and illustrativeexamples described herein, will be apparent to persons of ordinary skillin the art. All such modifications, variations, alternatives andequivalents are intended to be within the scope of the presentdisclosure and the appended claims.

Example 30 Fabricating a Stent and Treatment of Stent by Heat at aTemperature Above Tg Before Patterning, and then Crimping the Stent ontoa Delivery System at a Temperature Below Tg

A biodegradable stent comprising a polymeric material formed optionallyinto a tubular body wherein the polymeric material compriseslactide-co-caprolactone (or a blend of lactide and caprolactone). Thetubular body is formed optionally by spraying the polymeric materialonto a mandrel. DCM (or other suitable solvent capable of dissolvingcompletely the polymeric material) is incorporated into the solution tosuch that the amount of DCM after treatment is less than 1.5% by weightof the polymeric material. The tubular body is treated by heating at atemperature above Tg of the polymeric material for a time period rangingfrom 10 seconds to 5 hours, and/or cooling at a temperature below Tg ofthe polymeric material, is patterned at substantially the same diameteras the formed diameter, and is crimped onto a delivery system at atemperature below Tg of the polymeric material. The stent at bodytemperature (about 37 C) is expandable from the crimped configuration toan expanded diameter that is 1.2 times the nominal deployment diameter(labeled diameter) of the stent without fracture and having sufficientstrength to support a body lumen.

Example 31 Fabricating a Stent and Treatment of Stent at Substantiallythe Same Diameter of the Formed Polymeric Tube Outer Diameter, byPressure, Heat at a Temperature Above Tg, and Optionally Stretching;Before Patterning; and then Crimping the Stent onto a Delivery System ata Temperature Below Tg

A 4.00 mm outer diameter and 3.70 mm inner diameter polymeric tubecomprising 85:15 poly(L-lactide-co-glycolide) formed by extrusion,spraying, dipping, or the like. This tube is placed inside a metal (orglass mold) mold with approximately 4.0 mm diameter cylindrical hole(inner diameter of the mold), (or optionally 4.0 mm inner diameter mold,or optionally less than 4.0 mm ID mold, or optionally 4.1 mm ID mold, oroptionally a mold ID with 0.9-1.15 times the formed OD of the polymericmaterial, or optionally a mold ID with 0.9-1.1, times the formed OD ofthe polymeric material. The mold optionally could be composed of twohalve for ease of tube placement and removal. The mold and/or thepolymeric material is heated to above the polymeric material Tg. The IDof the polymeric material is pressurized at pressure(s) ranging from 100PSi to 5000 psi in a fraction of a second to 5 minutes, and thepolymeric material is optionally stretched by an amount ranging from 10%to 500% of the polymeric material length in a time ranging from afraction of a second to 5 minutes. The polymeric material is optionallycooled at a temperature below Tg in a time ranging from a fraction of asecond to 50 minutes. The compressed polymeric tubing with approximately4.00 mm outer diameter (+/−0.1 mm) and an Inner diameter ranging from3.8 to approximately 3.6 mm inner diameter is then removed. The wall ofthe polymeric tube in this example is compressed approximately 0.0005″.The modified tube is patterned at substantially the same diameter, andsubsequently coated with a drug/or drug-polymer and subsequently crimpedonto a delivery system at a temperature below Tg of the polymericmaterial and then sterilized. The stent at body temperature (about 37 C)is expandable from the crimped configuration to an expanded diameterhaving sufficient strength to support a body lumen.

Example 32 Novolimus Eluting Bioresorbable Coronary Stent System in thePorcine Model

Studies were performed in a porcine model with the Novolimus ElutingBioresorbable Coronary Stent System which combines a polymer stentcoated with a thin topcoat layer of polymer with Novolimus. The stentsin the studies comprised PLLA, PLLAPGA, PLLAPCL, Poly (Llactide-co-Glycolide) and poly(L lactide-co-caprolactone). At least oneof the studies is described below. The nominal drug dose in the coatingon the 18 mm length stent is 85 μg of Novolimus and coating ispoly(L-lactide-co-glycolide).

The purpose of the studies are to evaluate the efficacy and safety ofthe polymeric degradable drug eluting stent after a period of 1 m, 3 m,6 m, 9 m, 1 year and 2 years. The vascular response, including thearterial minimal lumen diameter and percent stenosis, will be evaluatedin all vessels using quantitative vessel angiography (QCA) at 1 m, 3 m,6 m, 9 m, 1 year and 2 years. Optical coherence tomography (OCT) willalso be performed at time points to assess stent apposition and recoil.Additionally, histopathologic analysis of the coronary arteries will beperformed at 1 m, 3 m, 6 m and 2 years to evaluate the cellular responseto the stents. Another purpose of this study is to evaluatepharmacokinetics (PK) of the released drug at 3 days, 7 days, 28±2 days,and longer timepoints; drug release will be assessed by analysis of thedrug remaining on the stents and uptake of the drug by the tissue.

A nonatherosclerotic swine model was chosen. Hybrid farm pigs(Landrance-Yorkshire) were selected for use in studies up to 3 m inlength and Yucatan Mini Swine were selected for use in the 6 m andlonger term studies due to starting size and growth expectations. Whenpossible, stents are implanted in the 3 coronary arteries (leftcircumflex artery [LCx], left anterior descending artery [LAD] and rightcoronary artery [RCA]), and in the left and right internal mammaryarteries (IMAs) per animal.

Upon assignment to the study and until sacrifice, animals will bemonitored and observed at least twice a day. To prevent or reduce theoccurrence of thrombotic events, animals are treated daily, withacetylsalicylic acid (325 mg, per os [PO]) and clopidogrel (300 mg onthe first day and 75 mg daily afterwards, PO), beginning at least 3 daysbefore intervention and continuing until sacrifice. The drugs will becrushed to powder and mixed with their food; therefore, treatment willnot be administered when animals are fasted. Fasting (food, includingany dietary supplements) will be conducted the morning prior tointerventional procedures and scheduled sacrifice. Water will not bewithheld. Animals will be tranquilized with ketamine, azaperone andatropine administered intramuscularly [IM]. Animal weight will berecorded. Anesthesia induction will be achieved with propofol injectedintravenously [IV]. Upon induction of light anesthesia, the subjectanimal will be intubated and supported with mechanical ventilation.Isoflurane in oxygen will be administered to maintain a surgical planeof anesthesia. Intravenous fluid therapy will be initiated andmaintained throughout the procedure. The rate may be increased toreplace blood loss or to correct low systemic blood pressure. To preventpostoperative infection, animals will be given prophylactic antibioticDraxxin® IM. Additional doses may be administered as deemed appropriate.In order to prevent pain sensitization and minimize postoperative pain,Torbugesic (butorphanol) will be administered IM as preemptiveanalgesia. After induction of anesthesia, the left or right femoralartery will be accessed through an incision made in the inguinal region.Bupivacain IM will be infiltrated into the femoral access site toachieve local anesthesia and manage pain after surgery. An arterialsheath will be introduced and advanced into the artery. An initialheparin bolus will be administered and ACT will be measured at leastevery 30 minutes and recorded. The device will not be introduced untilACT is confirmed to be >300 seconds. If ACT is <300 seconds, additionalheparin will be administered. Under fluoroscopic guidance, a guidingcatheter will be inserted through the sheath (6F) and advanced to theappropriate location. After placement of the guiding catheter,nitroglycerin will be delivered to achieve vasodilatation andangiographic images of the vessel will be obtained with contrast mediato identify the proper location for the deployment site (designatedpre-stent angiographies). A segment of coronary artery will be chosenand a guidewire will be inserted into the chosen artery. QCA will beperformed at this time to document the reference diameter for stentplacement. OCT will be performed before implantation to confirm vesselsizing at three locations per coronary vessel.

Stent Deployment Procedures: The stent will be introduced into theselected artery (diameter range of 2.6 to 3.0 mm if possible) byadvancing the delivery system through the guiding catheter, over theguide wire to the deployment site. After the stent enters the guidecatheter, there will be at least a one minute soak wait before deployingthe stent. The stent will then be deployed. The balloon will be inflatedat a slow rate: starting with 10 second intervals per atmosphere, bringthe balloon to 2 atm. Further expansion completed at 3-5 secondintervals for each subsequent atmosphere of pressure. This is approx.40-50 seconds to nominal pressure. Final pressure is maintained for20-30 seconds. An angiogram of the balloon at full inflation will berecorded (designated balloon angiography) and the inflation pressurewill be noted. After the target stent to artery ratio has been achieved,vacuum will be slowly applied to the inflation device to deflate theballoon. Complete balloon deflation will be verified fluoroscopically. Asecond inflation may be conducted if a stent is not well apposed againstarterial wall or if an animal is at risk. Injection of nitroglycerinwill be repeated and a final angiogram of the treated vessel will beperformed (designated post-stent angiography) to document devicepatency, and TIMI flow Implantation will be repeated in the othervessels.

OCT will be performed on animals to assess stent recoil. OCT will beperformed before implantation to confirm vessel sizing at threelocations per coronary vessel. After all implants are completed, OCTwill be performed again for the same (first) stent, followed by everyother stent implanted in the coronaries (designated end of implant OCT).

Following the successful deployment of stents and completion ofangiography, all catheters and the sheath will be removed from theanimal and the femoral artery will be ligated. The incision will beclosed in layers with appropriate suture materials. An antibioticointment will be applied to the wound.

The fluoroscopic output from the stent implantation (pre-stent, ballooninflation, post-stent, and end of implant) and at explantation (final)was recorded in digital format. From these images, QCA measurements wereobtained. OCT imaging was performed in animal after the first stent wasimplanted and after all implants had been completed. Severalsemi-quantitative parameters were employed to assess the biologicalresponse of vascular tissue to the stents by light microscopyexamination of stained sections. Other organ samples were observed forany abnormal findings.

What is claimed is:
 1. An expandable biodegradable stent, comprising: atubular biodegradable polymeric material, said expandable stent at bodytemperature being expandable from a crimped configuration to a deployedconfiguration in a body lumen and have sufficient strength to supportthe body lumen after an initial recoil from said deployed configuration,wherein the stent further expands to a second larger configuration. 2.The expandable stent of claim 1 wherein the polymeric material istreated to control one or more of crystallinity, T_(g), or molecularweight.
 3. The expandable stent of claim 2 wherein the polymericmaterial does not exhibit substantial phase separation after treatment.4. The expandable stent of claim 2 wherein the crystallinity iscontrolled at a level between 5%-30%.
 5. The expandable stent of claim 1wherein the body lumen has a first configuration after deployment of thestent which expands to a second larger configuration.
 6. The expandablestent of claim 5 wherein the body lumen expands to the second largerconfiguration between 1 month to 1 year.
 7. The expandable stent as inclaim 5 wherein the second expanded lumen configuration has a transversedimension of at least 5% greater than the transverse dimension of theinitial configuration.
 8. The expandable stent of claim 1 wherein thepolymeric material has a T_(g) between 37° C. and 44° C.
 9. Theexpandable stent of claim 1 wherein the polymeric material comprises atleast one co-polymer.
 10. The expandable stent of claim 9 wherein thepolymeric material further comprises one or more monomers or polymers.11. The expandable stent of claim 10 wherein the further one or moremonomers or polymers are blended with the at least one co-polymer of thepolymeric material.
 12. The expandable stent of claim 9 wherein thepolymeric material comprises 1 to 100 micrograms of monomers or polymersper milligram of polymeric material.
 13. The expandable stent of claim 1wherein the polymeric material has a molecular weight between 30 kDa and700 kDa.
 14. The expandable stent of claim 1 wherein the polymericmaterial is at least one material selected from the group consisting ofa polymer of lactic acid; a polymer of polyglycolic acid; a polymer ofpolylactic glycolic acid; a copolymer of a lactide and a glycolide;polylactide-co-polycaprolactone; a copolymer of glycolide andcaprolactone; a copolymer of a lactide, a glycolide and caprolactone;polycaprolactone; a blend of a lactide and a glycolide; a blend oflactide and caprolactone; a blend of a glycolide and caprolactone; and ablend of a lactide, a glycolide and caprolactone.
 15. The expandablestent of claim 1 wherein the polymeric material comprises 80-99% byweight of a lactide.
 16. The expandable stent of claim 1 wherein thepolymeric material comprises 1-20% by weight of a caprolactone.
 17. Theexpandable stent of claim 1 wherein the polymeric material furthercomprises 1-20% by weight of a glycolide.
 18. The expandable stent ofclaim 1 wherein the polymeric material further comprises between 0.1%and 10% (by weight) of at least one solvent.
 19. The expandable stent ofclaim 1 wherein the treatment comprises at least one of heating, heatingand cooling, cooling, solvent removal, solvent incorporation,pressurization with gas, exposure to radiation, or expansion of thepolymeric material to about 1 to 1.5 times a stent deployed diameter.20. The expandable stent of claim 19 wherein the treatment comprisesheating and cooling.
 21. The expandable stent of claim 20 wherein theheating temperature is above Tg of the polymeric material.
 22. Theexpandable stent of claim 1 wherein the polymeric material comprises atleast one monomer or polymer of: lactide, glycolide,polylactide-co-glycolide, caprolactone, polylactide-co-polycaprolactone,or polyglycolide-co-caprolactone.
 23. The expandable stent of claim 1wherein the stent self expands prior to expansion to the deployedconfiguration.
 24. The expandable stent of claim 1 wherein the stent hasinward recoil from the deployed configuration between 3% and 10%. 25.The expandable stent of claim 1 wherein the stent has a nominal expandedconfiguration with a transverse dimension and the deployed configurationhas a transverse dimension that is 1 to 1.5 times the transversedimension of the nominal expanded configuration.
 26. The expandablestent of claim 1 wherein the transverse dimension of the deployedconfiguration ranges from 3 mm to 25 mm.
 27. The expandable stent ofclaim 1 wherein the stent is expanded to the deployed configuration byballoon expansion.
 28. The expandable stent of claim 1 wherein thesecond expanded configuration has a transverse dimension of at least 5%greater than the transverse dimension of the deployed configuration. 29.The expandable stent as in claim 1 wherein the stent expands to thesecond expanded configuration between 1 month and 1 year.
 30. Theexpandable stent of claim 1 wherein the polymeric material has anelastic modulus ranging from 0.35 GPa to 1.5 GPa.